Skip to main content

Advertisement

SpringerLink
Log in

Computational Models to Assign Biopharmaceutics Drug Disposition Classification from Molecular Structure

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

We applied in silico methods to automatically classify drugs according to the Biopharmaceutics Drug Disposition Classification System (BDDCS).

Materials and Methods

Models were developed using machine learning methods including recursive partitioning (RP), random forest (RF) and support vector machine (SVM) algorithms with ChemDraw, clogP, polar surface area, VolSurf and MolConnZ descriptors. The dataset consisted of 165 training and 56 test set molecules.

Results

RF model 3, RP model 1, and SVM model 1 can correctly predict 73.1, 63.6 and 78.6% test compounds in classes 1, 2 and 3, respectively. Both RP and SVM models can be used for class 4 prediction. The inclusion of consensus analysis resulted in improved test set predictions for class 2 and 4 drugs.

Conclusions

The models can be used to predict BDDCS class for new compounds from molecular structure using readily available molecular descriptors and software, representing an area where in silico approaches could aid the pharmaceutical industry in speeding drugs to the patient and reducing costs. This could have significant applications in drug discovery to identify molecules that may have future developability issues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

BCS:

Biopharmaceutics Classification System

BDDCS:

Biopharmaceutics Drug Disposition Classification System

RF:

random forest

RP:

recursive partitioning

SVM:

support vector machine

References

  1. WHO. Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. FDA guidance for industry, federal drug and food administration, Rockville, MD (2002).

  2. H. H. Blume and B. S. Schug. The biopharmaceutics classification system (BCS): class III drugs—better candidates for BA/BE waiver? Eur. J. Pharm. Sci. 9:117–121 (1999).

    PubMed  CAS  Google Scholar 

  3. J. E. Polli, L. X. Yu, J. A. Cook, G. L. Amidon, R. T. Borchardt, B. A. Burnside, P. S. Burton, M. L. Chen, D. P. Conner, P. J. Faustino, A. A. Hawi, A. S. Hussain, H. N. Joshi, G. Kwei, V. H. Lee, L. J. Lesko, R. A. Lipper, A. E. Loper, S. G. Nerurkar, J. W. Polli, D. R. Sanvordeker, R. Taneja, R. S. Uppoor, C. S. Vattikonda, I. Wilding, and G. Zhang. Summary workshop report: biopharmaceutics classification system-implementation challenges and extension opportunities. J. Pharm. Sci. 93:1375–1381 (2004).

    PubMed  CAS  Google Scholar 

  4. N. A. Kasim, M. Whitehouse, C. Ramachandran, M. Bermejo, H. Lennernas, A. S. Hussain, H. E. Junginger, S. A. Stavchansky, K. K. Midha, V. P. Shah, and G. L. Amidon. Molecular properties of WHO essential drugs and provisional biopharmaceutical classification. Mol. Pharm. 1:85–96 (2004).

    PubMed  CAS  Google Scholar 

  5. M. Lindenberg, S. Kopp, and J. B. Dressman. Classification of orally administered drugs on the World Health Organization Model list of Essential Medicines according to the biopharmaceutics classification system. Eur. J. Pharm. Biopharm. 58:265–278 (2004).

    PubMed  Google Scholar 

  6. C. Y. Wu and L. Z. Benet. Predicting drug disposition via application of BCS: transport/absorption/ elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm. Res. 22:11–23 (2005).

    PubMed  CAS  Google Scholar 

  7. T. Takagi, C. Ramachandran, M. Bermejo, S. Yamashita, L. X. Yu, and G. L. Amidon. A provisional biopharmaceutical classification of the top 200 oral drug products in the United States, Great Britain, Spain, and Japan. Mol. Pharm. 3:631–643 (2006).

    PubMed  CAS  Google Scholar 

  8. S. Ekins, C. L. Waller, P. W. Swaan, G. Cruciani, S. A. Wrighton, and J. H. Wikel. Progress in predicting human ADME parameters in silico. J. Pharmacol. Toxicol. Methods. 44:251–272 (2000).

    PubMed  CAS  Google Scholar 

  9. S. Ekins and P. W. Swaan. Computational models for enzymes, transporters, channels and receptors relevant to ADME/TOX. Rev. Comp. Chem. 20:333–415 (2004).

    CAS  Google Scholar 

  10. J. B. Ed. by Dressman. Proposal to waive in vivo bioequivalence requirements for the WHO model list of essential medicines immediate release, solid oral dosage forms. World Health Organization (2005).

  11. Merck. The Merck Index, Merck Research Laboratories, Rahway, NJ. The Merck Index, Merck Research Laboratories, Rahway, NJ 13th Edition:(2001).

  12. USP. USP DI Vol III, Approved drug products and legal requirements, 18th Ed., United States Pharmacopoeial Convention Inc., Rockville, MD. 1998. (1998).

  13. USP. The United State Pharmacopoeia, 24th Ed., by authority of the United State Pharmacopoeial convention, Inc., Printed by National Publishing, Philadelphia, PA, 2000. (2000).

  14. D. M. Oh, R. L. Curl, and G. L. Amidon. Estimating the fraction dose absorbed from suspensions of poorly soluble compounds in humans: a mathematical model. Pharm. Res. 10:264–270 (1993).

    PubMed  CAS  Google Scholar 

  15. D. S. Wishart, C. Knox, A. C. Guo, S. Shrivastava, M. Hassanali, P. Stothard, Z. Chang, and J. Woolsey. DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 34:D668–672 (2006).

    PubMed  CAS  Google Scholar 

  16. M. Clark, R. D. Cramer, and N. van Op den Bosch. Validation of the general purpose Tripos 5.2 force field. J. Comput. Chem. 10:982–1012 (1989).

    CAS  Google Scholar 

  17. G. Cruciani, P. Crivori, P.-A. Carrupt, B. Testa. Molecular fields in quantitative structure-permeation relationships:the volSurf approach. THEOCHEM. 503:17–30 (2000).

    CAS  Google Scholar 

  18. L. B. Kier and L. H. Hall. Molecular Connectivity in Structure-Activity Analysis. Wiley, Letchworth, Hertfordshire, England, (1986).

    Google Scholar 

  19. T. M. Therneau and E.J. Atkinson. An introduction to recursive partitioning using the RPART routines, Department of health Sciences Research: Mayo clinic, (1997).

  20. A. Liaw and M. Wiener. Classification and regression by random forest. R. News. 2/3:18–22 (2002).

    Google Scholar 

  21. M. I. Walton, C. R. Wolf, and P. Workman. Molecular enzymology of the reductive bioactivation of hypoxic cell cytotoxins. Int. J. Radiat. Oncol. Biol. Phys. 16:983–986 (1989).

    PubMed  CAS  Google Scholar 

  22. P. Workman, R. A. White, M. I. Walton, L. N. Owen, and P. R. Twentyman. Preclinical pharmacokinetics of benznidazole. Br. J. Cancer. 50:291–303 (1984).

    PubMed  CAS  Google Scholar 

  23. P. E. Golstein, A. Boom, J. van Geffel, P. Jacobs, B. Masereel, and R. Beauwens. P-glycoprotein inhibition by glibenclamide and related compounds. Pflugers. Arch. 437:652–660 (1999).

    PubMed  CAS  Google Scholar 

  24. Y. Naritomi, S. Terashita, and A. Kagayama. Identification and relative contributions of human cytochrome P450 isoforms involved in the metabolism of glibenclamide and lansoprazole: evaluation of an approach based on the in vitro substrate disappearance rate. Xenobiotica. 34:415–427 (2004).

    PubMed  CAS  Google Scholar 

  25. R. T. Gilman A. G., Nies, A. S., and P. Taylor. Goodman and Gilman’s The pharmacological basis of therapeutics., Pergamon Press, (1990).

  26. J. Wijnholds, C. A. Mol, L. van Deemter, M. de Haas, G. L. Scheffer, F. Baas, J. H. Beijnen, R. J. Scheper, S. Hatse, E. De Clercq, J. Balzarini, and P. Borst. Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs. Proc. Natl. Acad. Sci. U. S. A. 97:7476–7481 (2000).

    PubMed  CAS  Google Scholar 

  27. T. M. Davis, T. Q. Binh, L. T. Thu, R. Rossi, P. T. Danh, P. H. Barrett, and J. Beilby. Pharmacokinetics of retinyl palmitate and retinol after intramuscular retinyl palmitate administration in severe malaria. Clin. Sci. (Lond). 99:433–441 (2000).

    CAS  Google Scholar 

  28. E. Liang, J. Proudfoot, and M. Yazdanian. Mechanisms of transport and structure–permeability relationship of sulfasalazine and its analogs in Caco-2 cell monolayers. Pharm. Res. 17:1168–1174 (2000).

    PubMed  CAS  Google Scholar 

  29. H. Zaher, A. A. Khan, J. Palandra, T. G. Brayman, L. Yu, and J. A. Ware. Breast cancer resistance protein (Bcrp/abcg2) is a major determinant of sulfasalazine absorption and elimination in the mouse. Mol. Pharm. 3:55–61 (2006).

    PubMed  CAS  Google Scholar 

  30. S. E. O’Brien and M. J. de Groot. Greater than the sum of its parts: combining models for useful ADMET prediction. J. Med. Chem. 48:1287–1291 (2005).

    PubMed  CAS  Google Scholar 

  31. G. L. Amidon, H. Lennernas, V. P. Shah, and J. R. Crison. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm. Res. 12:413–420 (1995).

    PubMed  CAS  Google Scholar 

  32. C. Chang, P. M. Bahadduri, J. E. Polli, P. W. Swaan, and S. Ekins. Rapid identification of P-glycoprotein substrates and inhibitors. Drug Metab. Dispos. 34:1976–1984 (2006).

    PubMed  CAS  Google Scholar 

  33. C. A. Bergstrom. In silico predictions of drug solubility and permeability: two rate-limiting barriers to oral drug absorption. Basic Clin. Pharmacol. Toxicol. 96:156–161 (2005).

    PubMed  Google Scholar 

  34. C. A. Bergstrom, M. Strafford, L. Lazorova, A. Avdeef, K. Luthman, and P. Artursson. Absorption classification of oral drugs based on molecular surface properties. J. Med. Chem. 46:558–570 (2003).

    PubMed  Google Scholar 

  35. J. Baldoni. Roles of BCS in drug development, AAPS Workshop on BE, BCS and Beyond, Bethesda, MD, (2007).

  36. X. P. Chen, Z. R. Tan, S. L. Huang, Z. Huang, D. S. Ou-Yang, and H. H. Zhou. Isozyme-specific induction of low-dose aspirin on cytochrome P450 in healthy subjects. Clin. Pharmacol. Ther. 73:264–271 (2003).

    PubMed  CAS  Google Scholar 

  37. G. Levy and T. Tsuchiya. Salicylate accumulation kinetics in man. N. Engl. J. Med. 287:430–432 (1972).

    Article  PubMed  CAS  Google Scholar 

  38. S. Nishio, H. Watanabe, K. Kosuge, S. Uchida, H. Hayashi, and K. Ohashi. Interaction between amlodipine and simvastatin in patients with hypercholesterolemia and hypertension. Hypertens. Res. 28:223–227 (2005).

    PubMed  CAS  Google Scholar 

  39. T. Kuzuya, T. Kobayashi, N. Moriyama, T. Nagasaka, I. Yokoyama, K. Uchida, A. Nakao, and T. Nabeshima. Amlodipine, but not MDR1 polymorphisms, alters the pharmacokinetics of cyclosporine A in Japanese kidney transplant recipients. Transplantation. 76:865–868 (2003).

    PubMed  CAS  Google Scholar 

  40. P. A. Meredith and H. L. Elliott. Clinical pharmacokinetics of amlodipine. Clin. Pharmacokinet. 22:22–31 (1992).

    PubMed  CAS  Google Scholar 

  41. R. L. Walsky and R. S. Obach. Validated assays for human cytochrome P450 activities. Drug Metab. Dispos. 32:647–660 (2004).

    PubMed  CAS  Google Scholar 

  42. P. Winstanley, G. Edwards, M. Orme, and A. Breckenridge. The disposition of amodiaquine in man after oral administration. Br. J. Clin. Pharmacol. 23:1–7 (1987).

    PubMed  CAS  Google Scholar 

  43. N. J. White, M. van Vugt, and F. Ezzet. Clinical pharmacokinetics and pharmacodynamics and pharmacodynamics of artemether-lumefantrine. Clin. Pharmacokinet. 37:105–125 (1999).

    PubMed  CAS  Google Scholar 

  44. V. Navaratnam, S. M. Mansor, N. W. Sit, J. Grace, Q. Li, and P. Olliaro. Pharmacokinetics of artemisinin-type compounds. Clin. Pharmacokinet. 39:255–270 (2000).

    PubMed  CAS  Google Scholar 

  45. M. A. van Agtmael, C. A. Van Der Graaf, T. K. Dien, R. P. Koopmans, and C. J. van Boxtel. The contribution of the enzymes CYP2D6 and CYP2C19 in the demethylation of artemether in healthy subjects. Eur. J. Drug Metab. Pharmacokinet. 23:429–436 (1998).

    PubMed  Google Scholar 

  46. G. Lefevre, S. Looareesuwan, S. Treeprasertsuk, S. Krudsood, U. Silachamroon, I. Gathmann, R. Mull, and R. Bakshi. A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand. Am. J. Trop. Med. Hyg. 64:247–256 (2001).

    PubMed  CAS  Google Scholar 

  47. P. J. de Vries, and T. K. Dien. Clinical pharmacology and therapeutic potential of artemisinin and its derivatives in the treatment of malaria. Drugs. 52:818–836 (1996).

    PubMed  Google Scholar 

  48. X. Q. Li, A. Bjorkman, T. B. Andersson, L. L. Gustafsson, and C. M. Masimirembwa. Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur. J. Clin. Pharmacol. 59:429–442 (2003).

    PubMed  CAS  Google Scholar 

  49. P. Reungpatthanaphong, and S. Mankhetkorn. Modulation of multidrug resistance by artemisinin, artesunate and dihydroartemisinin in K562/adr and GLC4/adr resistant cell lines. Biol. Pharm. Bull. 25:1555–1561 (2002).

    PubMed  CAS  Google Scholar 

  50. N. J. White. Clinical pharmacokinetics and pharmacodynamics of artemisinin and derivatives. Trans. R. Soc. Trop. Med. Hyg. 88 Suppl 1:S41–43 (1994).

    PubMed  Google Scholar 

  51. D. Hornig. Metabolism and requirements of ascorbic acid in man. S. Afr. Med. J. 60:818–823 (1981).

    PubMed  CAS  Google Scholar 

  52. R. P. van Heeswijk, C. L. Cooper, B. C. Foster, B. M. Chauhan, F. Shirazi, I. Seguin, E. J. Phillips, and E. Mills. Effect of high-dose vitamin C on hepatic cytochrome P450 3A4 activity. Pharmacotherapy. 25:1725–1728 (2005).

    PubMed  Google Scholar 

  53. C. D. Chiang, E. J. Song, V. C. Yang, and C. C. Chao. Ascorbic acid increases drug accumulation and reverses vincristine resistance of human non-small-cell lung-cancer cells. Biochem. J. 301(Pt 3):759–764 (1994).

    PubMed  CAS  Google Scholar 

  54. M. Hollmann, E. Brode, G. Greger, H. Muller-Peltzer, and N. Wetzelsberger. Biperiden effects and plasma levels in volunteers. Eur. J. Clin. Pharmacol. 27:619–621 (1984).

    PubMed  CAS  Google Scholar 

  55. S. Kudo, and M. Odomi. Involvement of human cytochrome P450 3A4 in reduced haloperidol oxidation. Eur. J. Clin. Pharmacol. 54:253–259 (1998).

    PubMed  CAS  Google Scholar 

  56. R. Grimaldi, E. Perucca, G. Ruberto, C. Gelmi, F. Trimarchi, M. Hollmann, and A. Crema. Pharmacokinetic and pharmacodynamic studies following the intravenous and oral administration of the antiparkinsonian drug biperiden to normal subjects. Eur. J. Clin. Pharmacol. 29:735–737 (1986).

    PubMed  CAS  Google Scholar 

  57. S. A. Factor, W. J. Weiner, and F. Hefti. Acetaminophen metabolism by cytochrome P450 monooxygenases in Parkinson’s disease. Ann. Neurol. 26:286–288 (1989).

    PubMed  CAS  Google Scholar 

  58. S. Vickers, E. K. Stuart, J. R. Bianchine, H. B. Hucker, M. E. Jaffe, R. E. Rhodes, and W. J. Vandenheuvel. Metabolism of carbidopa (1-(−)-alpha-hydrazino-3,4-dihydroxy-alpha-methylhydrocinnamic acid monohydrate), an aromatic amino acid decarboxylase inhibitor, in the rat, rhesus monkey, and man. Drug Metab. Dispos. 2:9–22 (1974).

    PubMed  CAS  Google Scholar 

  59. J. Barre. [Pharmacokinetic properties of cefixime]. Presse. Med. 18:1578–1582 (1989).

    PubMed  CAS  Google Scholar 

  60. T. Niwa, T. Shiraga, T. Hashimoto, and A. Kagayama. Effect of cefixime and cefdinir, oral cephalosporins, on cytochrome P450 activities in human hepatic microsomes. Biol. Pharm. Bull. 27:97–99 (2004).

    PubMed  CAS  Google Scholar 

  61. W. F. Marshall, and J. E. Blair. The cephalosporins. Mayo Clin. Proc. 74:187–195 (1999).

    PubMed  CAS  Google Scholar 

  62. U. Loos, E. Musch, M. Malek, and E. Riedel. Comparative pharmacokinetics of chlorambucil and prednimustine after oral administration. Oncology. 48:334–342 (1991).

    PubMed  CAS  Google Scholar 

  63. M. Baumhakel, D. Kasel, R. A. Rao-Schymanski, R. Bocker, K. T. Beckurts, M. Zaigler, D. Barthold, and U. Fuhr. Screening for inhibitory effects of antineoplastic agents on CYP3A4 in human liver microsomes. Int. J. Clin. Pharmacol. Ther. 39:517–528 (2001).

    PubMed  CAS  Google Scholar 

  64. C. S. Morrow, P. K. Smitherman, S. K. Diah, E. Schneider, and A. J. Townsend. Coordinated action of glutathione S-transferases (GSTs) and multidrug resistance protein 1 (MRP1) in antineoplastic drug detoxification. Mechanism of GST A1-1- and MRP1-associated resistance to chlorambucil in MCF7 breast carcinoma cells. J. Biol. Chem. 273:20114–20120 (1998).

    PubMed  CAS  Google Scholar 

  65. G. C. Bolton, G. D. Allen, B. E. Davies, C. W. Filer, and D. J. Jeffery. The disposition of clavulanic acid in man. Xenobiotica. 16:853–863 (1986).

    Article  PubMed  CAS  Google Scholar 

  66. M. A. Wynalda, J. M. Hutzler, M. D. Koets, T. Podoll, and L. C. Wienkers. in vitro metabolism of clindamycin in human liver and intestinal microsomes. Drug Metab. Dispos. 31:878–887 (2003).

    PubMed  CAS  Google Scholar 

  67. D. Mazur, B. S. Schug, G. Evers, V. Larsimont, H. Fieger-Buschges, W. Gimbel, A. Keilbach-Bermann, and H. H. Blume. Bioavailability and selected pharmacokinetic parameters of clindamycin hydrochloride after administration of a new 600 mg tablet formulation. Int. J. Clin. Pharmacol. Ther. 37:386–392 (1999).

    PubMed  CAS  Google Scholar 

  68. U. S. Rao, R. L. Fine, and G. A. Scarborough. Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem. Pharmacol. 48:287–292 (1994).

    PubMed  CAS  Google Scholar 

  69. T. J. Mikkelson, P. D. Kroboth, W. J. Cameron, L. W. Dittert, V. Chungi, and P. J. Manberg. Single-dose pharmacokinetics of clomiphene citrate in normal volunteers. Fertil. Steril. 46:392–396 (1986).

    PubMed  CAS  Google Scholar 

  70. D. Ardid, and G. Guilbaud. Antinociceptive effects of acute and ‘chronic’ injections of tricyclic antidepressant drugs in a new model of mononeuropathy in rats. Pain. 49:279–287 (1992).

    PubMed  CAS  Google Scholar 

  71. A. Nagy, and R. Johansson. The demethylation of imipramine and clomipramine as apparent from their plasma kinetics. Psychopharmacology (Berl). 54:125–131 (1977).

    CAS  Google Scholar 

  72. L. E. Evans, J. H. Bett, J. R. Cox, J. P. Dubois, and T. Van Hees. The bioavailability of oral and parenteral chlorimipramine (Anafranil). Prog. Neuropsychopharmacol. 4:293–302 (1980).

    PubMed  CAS  Google Scholar 

  73. A. E. Balant-Gorgia, M. Gex-Fabry, and L. P. Balant. Clinical pharmacokinetics of clomipramine. Clin. Pharmacokinet. 20:447–462 (1991).

    PubMed  CAS  Google Scholar 

  74. C. A. Knupp, W. C. Shyu, R. Dolin, F. T. Valentine, C. McLaren, R. R. Martin, K. A. Pittman, and R. H. Barbhaiya. Pharmacokinetics of didanosine in patients with acquired immunodeficiency syndrome or acquired immunodeficiency syndrome-related complex. Clin. Pharmacol. Ther. 49:523–535 (1991).

    Article  PubMed  CAS  Google Scholar 

  75. S. Kaul, W. C. Shyu, U. A. Shukla, K. A. Dandekar, and R. H. Barbhaiya. Absorption, disposition, and metabolism of [14C]didanosine in the beagle dog. Drug Metab. Dispos. 21:447–453 (1993).

    PubMed  CAS  Google Scholar 

  76. N. Shiraki, A. Hamada, K. Yasuda, J. Fujii, K. Arimori, and M. Nakano. Inhibitory effect of human immunodeficiency virus protease inhibitors on multidrug resistance transporter P-glycoproteins. Biol. Pharm. Bull. 23:1528–1531 (2000).

    PubMed  CAS  Google Scholar 

  77. C. A. Joseph, and P. A. Dixon. A possible cytochrome P-450-mediated N-oxidation of diethylcarbamazine. J. Pharm. Pharmacol. 36:711–712 (1984).

    PubMed  CAS  Google Scholar 

  78. K. L. Mealey, R. Barhoumi, R. C. Burghardt, S. Safe, and D. T. Kochevar. Doxycycline induces expression of P glycoprotein in MCF-7 breast carcinoma cells. Antimicrob. Agents Chemother. 46:755–761 (2002).

    PubMed  CAS  Google Scholar 

  79. G. R. Bailie, and C. A. Johnson. Comparative review of the pharmacokinetics of vitamin D analogues. Semin. Dial. 15:352–357 (2002).

    PubMed  Google Scholar 

  80. S. A. a. D. E. Rangel-Castro I.J. The ergocalciferol content of dried pigmented and albino Cantharellus cibarius fruit bodies. Mycological Research. 106:70–73 (2002).

  81. K. E. Thummel, C. Brimer, K. Yasuda, J. Thottassery, T. Senn, Y. Lin, H. Ishizuka, E. Kharasch, J. Schuetz, and E. Schuetz. Transcriptional control of intestinal cytochrome P-4503A by 1alpha,25-dihydroxy vitamin D3. Mol. Pharmacol. 60:1399–1406 (2001).

    PubMed  CAS  Google Scholar 

  82. S. W. Park, N. Lomri, L. A. Simeoni, J. P. Fruehauf, and E. Mechetner. Analysis of P-glycoprotein-mediated membrane transport in human peripheral blood lymphocytes using the UIC2 shift assay. Cytometry. A. 53:67–78 (2003).

    PubMed  Google Scholar 

  83. J. L. Sommerfeldt, J. L. Napoli, E. T. Littledike, D. C. Beitz, and R. L. Horst. Metabolism of orally administered [3H]ergocalciferol and [3H]cholecalciferol by dairy calves. J. Nutr. 113:2595–2600 (1983).

    PubMed  CAS  Google Scholar 

  84. C. S. Lee, J. G. Gambertoglio, D. C. Brater, and L. Z. Benet. Kinetics of oral ethambutol in the normal subject. Clin. Pharmacol. Ther. 22:615–621 (1977).

    PubMed  CAS  Google Scholar 

  85. Y. Nishimura, N. Kurata, E. Sakurai, and H. Yasuhara. Inhibitory effect of antituberculosis drugs on human cytochrome P450-mediated activities. J. Pharmacol. Sci. 96:293–300 (2004).

    PubMed  CAS  Google Scholar 

  86. M. J. Ruse, and R. H. Waring. The effect of methimazole on thioamide bioactivation and toxicity. Toxicol. Lett. 58:37–41 (1991).

    PubMed  CAS  Google Scholar 

  87. M. Giaccone, A. Bartoli, G. Gatti, R. Marchiselli, F. Pisani, M. A. Latella, and E. Perucca. Effect of enzyme inducing anticonvulsants on ethosuximide pharmacokinetics in epileptic patients. Br. J. Clin. Pharmacol. 41:575–579 (1996).

    PubMed  CAS  Google Scholar 

  88. K. Bachmann, C. A. Chu, and V. Greear. In vivo evidence that ethosuximide is a substrate for cytochrome P450IIIA. Pharmacology. 45:121–128 (1992).

    Article  PubMed  CAS  Google Scholar 

  89. K. Bachmann, Y. He, J. G. Sarver, and N. Peng. Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of ethosuximide by human hepatic microsomal enzymes. Xenobiotica. 33:265–276 (2003).

    PubMed  CAS  Google Scholar 

  90. A. Crowe, and Y. K. Teoh. Limited P-glycoprotein mediated efflux for anti-epileptic drugs. J. Drug Target. 14:291–300 (2006).

    PubMed  CAS  Google Scholar 

  91. R. A. Tokola, and P. J. Neuvonen. Pharmacokinetics of antiepileptic drugs. Acta Neurol. Scand. Suppl. 97:17–27 (1983).

    PubMed  CAS  Google Scholar 

  92. R. D. Smyth, M. Pfeffer, A. Scalzo, and R. L. Comis. Bioavailability and pharmacokinetics of etoposide (VP-16). Semin. Oncol. 12:48–51 (1985).

    PubMed  CAS  Google Scholar 

  93. D. J. Stewart, D. Nundy, J. A. Maroun, L. Tetreault, and J. Prior. Bioavailability, pharmacokinetics, and clinical effects of an oral preparation of etoposide. Cancer Treat. Rep. 69:269–273 (1985).

    PubMed  CAS  Google Scholar 

  94. J. M. van Maanen, J. de Vries, D. Pappie, E. van den Akker, V. M. Lafleur, J. Retel, J. van der Greef, and H. M. Pinedo. Cytochrome P-450-mediated O-demethylation: a route in the metabolic activation of etoposide (VP-16-213). Cancer Res. 47:4658–4662 (1987).

    PubMed  Google Scholar 

  95. B. L. Leu, and J. D. Huang. Inhibition of intestinal P-glycoprotein and effects on etoposide absorption. Cancer Chemother. Pharmacol. 35:432–436 (1995).

    PubMed  CAS  Google Scholar 

  96. G. Inselmann, U. Holzlohner, and H. T. Heidemann. Effect of 5-fluorocytosine and 5-fluorouracil on human and rat hepatic cytochrome P 450. Mycoses. 32:638–643 (1989).

    Article  PubMed  CAS  Google Scholar 

  97. D. de Graaf, R. C. Sharma, E. B. Mechetner, R. T. Schimke, and I. B. Roninson. P-glycoprotein confers methotrexate resistance in 3T6 cells with deficient carrier-mediated methotrexate uptake. Proc. Natl. Acad. Sci. U. S. A. 93:1238–1242 (1996).

    PubMed  Google Scholar 

  98. A. J. Clifford, A. Arjomand, S. R. Dueker, P. D. Schneider, B. A. Buchholz, and J. S. Vogel. The dynamics of folic acid metabolism in an adult given a small tracer dose of 14C-folic acid. Adv. Exp. Med. Biol. 445:239–251 (1998).

    PubMed  CAS  Google Scholar 

  99. L. Balant, J. Fabre, and G. R. Zahnd. Comparison of the pharmacokinetics of glipizide and glibenclamide in man. Eur. J. Clin. Pharmacol. 8:63–69 (1975).

    PubMed  CAS  Google Scholar 

  100. M. Develoux. [Griseofulvin]. Ann. Dermatol. Venereol. 128:1317–1325 (2001).

    PubMed  CAS  Google Scholar 

  101. E. O. Farombi, O. Akinloye, C. O. Akinmoladun, and G. O. Emerole. Hepatic drug metabolizing enzyme induction and serum triacylglycerol elevation in rats treated with chlordiazepoxide, griseofulvin, rifampicin and phenytoin. Clin. Chim. Acta. 289:1–10 (1999).

    PubMed  CAS  Google Scholar 

  102. S. Kives, P. M. Hahn, E. White, F. Z. Stanczyk, and R. L. Reid. Bioavailability of the Yuzpe and levonorgestrel regimens of emergency contraception: vaginal vs. oral administration. Contraception. 71:197–201 (2005).

    PubMed  CAS  Google Scholar 

  103. V. Hatorp, K. T. Hansen, and M. S. Thomsen. Influence of drugs interacting with CYP3A4 on the pharmacokinetics, pharmacodynamics, and safety of the prandial glucose regulator repaglinide. J. Clin. Pharmacol. 43:649–660 (2003).

    PubMed  CAS  Google Scholar 

  104. M. Frohlich, N. Albermann, A. Sauer, I. Walter-Sack, W. E. Haefeli, and J. Weiss. In vitro and ex vivo evidence for modulation of P-glycoprotein activity by progestins. Biochem. Pharmacol. 68:2409–2416 (2004).

    PubMed  Google Scholar 

  105. F. Z. Stanczyk, and S. Roy. Metabolism of levonorgestrel, norethindrone, and structurally related contraceptive steroids. Contraception. 42:67–96 (1990).

    PubMed  CAS  Google Scholar 

  106. H. R. Maxon, W. A. Ritschel, C. P. Volle, M. A. Eldon, I. W. Chen, M. F. Fernandez, J. Cline, and G. Mayfield. Pilot study on the absolute and relative bioavailability of Synthroid and Levothroid, two brands of sodium levothyroxine. Int. J. Clin. Pharmacol. Ther. Toxicol. 21:379–382 (1983).

    PubMed  CAS  Google Scholar 

  107. C. Liddle, B. J. Goodwin, J. George, M. Tapner, and G. C. Farrell. Separate and interactive regulation of cytochrome P450 3A4 by triiodothyronine, dexamethasone, and growth hormone in cultured hepatocytes. J. Clin. Endocrinol. Metab. 83:2411–2416 (1998).

    PubMed  CAS  Google Scholar 

  108. T. Mitin, L. L. Von Moltke, M. H. Court, and D. J. Greenblatt. Levothyroxine up-regulates P-glycoprotein independent of the pregnane X receptor. Drug Metab. Dispos. 32:779–782 (2004).

    PubMed  CAS  Google Scholar 

  109. P. T. Giao, and P. J. de Vries. Pharmacokinetic interactions of antimalarial agents. Clin. Pharmacokinet. 40:343–373 (2001).

    PubMed  CAS  Google Scholar 

  110. F. Ezzet, R. Mull, and J. Karbwang. Population pharmacokinetics and therapeutic response of CGP 56697 (artemether + benflumetol) in malaria patients. Br. J. Clin. Pharmacol. 46:553–561 (1998).

    PubMed  CAS  Google Scholar 

  111. J. M. Wright, M. Orozco-Gonzalez, G. Polak, and C. T. Dollery. Duration of effect of single daily dose methyldopa therapy. Br. J. Clin. Pharmacol. 13:847–854 (1982).

    PubMed  CAS  Google Scholar 

  112. E. Myhre, H. E. Rugstad, and T. Hansen. Clinical pharmacokinetics of methyldopa. Clin. Pharmacokinet. 7:221–233 (1982).

    PubMed  CAS  Google Scholar 

  113. G. R. Haenen, F. P. Jansen, N. P. Vermeulen, and A. Bast. Activation of the microsomal glutathione S-transferase by metabolites of alpha-methyldopa. Arch. Biochem. Biophys. 287:48–52 (1991).

    PubMed  CAS  Google Scholar 

  114. O. Heikinheimo. Clinical pharmacokinetics of mifepristone. Clin. Pharmacokinet. 33:7–17 (1997).

    PubMed  CAS  Google Scholar 

  115. G. R. Jang, S. A. Wrighton, and L. Z. Benet. Identification of CYP3A4 as the principal enzyme catalyzing mifepristone (RU 486) oxidation in human liver microsomes. Biochem. Pharmacol. 52:753–761 (1996).

    PubMed  CAS  Google Scholar 

  116. O. Fardel, A. Courtois, B. Drenou, T. Lamy, V. Lecureur, P. Y. le Prise, and R. Fauchet. Inhibition of P-glycoprotein activity in human leukemic cells by mifepristone. Anticancer Drugs. 7:671–677 (1996).

    PubMed  CAS  Google Scholar 

  117. P. J. Hoskin, G. W. Hanks, G. W. Aherne, D. Chapman, P. Littleton, and J. Filshie. The bioavailability and pharmacokinetics of morphine after intravenous, oral and buccal administration in healthy volunteers. Br. J. Clin. Pharmacol. 27:499–505 (1989).

    PubMed  CAS  Google Scholar 

  118. D. Projean, P. E. Morin, T. M. Tu, and J. Ducharme. Identification of CYP3A4 and CYP2C8 as the major cytochrome P450 s responsible for morphine N-demethylation in human liver microsomes. Xenobiotica. 33:841–854 (2003).

    PubMed  CAS  Google Scholar 

  119. S. P. Letrent, J. W. Polli, J. E. Humphreys, G. M. Pollack, K. R. Brouwer, and K. L. Brouwer. P-glycoprotein-mediated transport of morphine in brain capillary endothelial cells. Biochem. Pharmacol. 58:951–957 (1999).

    PubMed  CAS  Google Scholar 

  120. E. D. Kharasch, C. Hoffer, D. Whittington, and P. Sheffels. Role of P-glycoprotein in the intestinal absorption and clinical effects of morphine. Clin. Pharmacol. Ther. 74:543–554 (2003).

    PubMed  CAS  Google Scholar 

  121. T. E. Bapiro, A. C. Egnell, J. A. Hasler, and C. M. Masimirembwa. Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab. Dispos. 29:30–35 (2001).

    PubMed  CAS  Google Scholar 

  122. A. Rojas, R. J. Hodgkiss, M. R. Stratford, M. F. Dennis, and H. Johns. Pharmacokinetics of varying doses of nicotinamide and tumour radiosensitisation with carbogen and nicotinamide: clinical considerations. Br. J. Cancer. 68:1115–1121 (1993).

    PubMed  CAS  Google Scholar 

  123. A. Petley, B. Macklin, A. G. Renwick, and T. J. Wilkin. The pharmacokinetics of nicotinamide in humans and rodents. Diabetes. 44:152–155 (1995).

    PubMed  CAS  Google Scholar 

  124. G. La Piana, D. Marzulli, M. I. Consalvo, and N. E. Lofrumento. Cytochrome c-induced cytosolic nicotinamide adenine dinucleotide oxidation, mitochondrial permeability transition, and apoptosis. Arch. Biochem. Biophys. 410:201–211 (2003).

    PubMed  Google Scholar 

  125. S. Zhou, S. Yung Chan, B. Cher Goh, E. Chan, W. Duan, M. Huang, and H. L. McLeod. Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs. Clin. Pharmacokinet. 44:279–304 (2005).

    PubMed  CAS  Google Scholar 

  126. M. E. Letelier, P. Izquierdo, L. Godoy, A. M. Lepe, and M. Faundez. Liver microsomal biotransformation of nitro-aryl drugs: mechanism for potential oxidative stress induction. J. Appl. Toxicol. 24:519–525 (2004).

    PubMed  CAS  Google Scholar 

  127. S. M. Murta, W. G. dos Santos, C. Anacleto, P. Nirde, E. S. Moreira, and A. J. Romanha. Drug resistance in Trypanosoma cruzi is not associated with amplification or overexpression of P-glycoprotein (PGP) genes. Mol. Biochem. Parasitol. 117:223–228 (2001).

    PubMed  CAS  Google Scholar 

  128. C. Paulos, J. Paredes, I. Vasquez, S. Thambo, A. Arancibia, and G. Gonzalez-Martin. Pharmacokinetics of a nitrofuran compound, nifurtimox, in healthy volunteers. Int. J. Clin. Pharmacol. Ther. Toxicol. 27:454–457 (1989).

    PubMed  CAS  Google Scholar 

  129. R. K. Liedtke, S. Ebel, B. Missler, W. Haase, and L. Stein. Single-dose pharmacokinetics of macrocrystalline nitrofurantoin formulations. Arzneimittelforschung. 30:833–836 (1980).

    PubMed  CAS  Google Scholar 

  130. V. Leskovac, and M. Popovic. Mechanism of reduction of nitrofurantoin on liver microsomes. Pharmacol. Res. Commun. 12:13–27 (1980).

    PubMed  CAS  Google Scholar 

  131. J. D. Conklin. The pharmacokinetics of nitrofurantoin and its related bioavailability. Antibiot. Chemother. 25:233–252 (1978).

    PubMed  CAS  Google Scholar 

  132. H. R. Kwon, P. Green, and S. H. Curry. Pharmacokinetics of nitroglycerin and its metabolites after administration of sustained-release tablets. Biopharm. Drug Dispos. 13:141–152 (1992).

    PubMed  CAS  Google Scholar 

  133. N. H. Lee, and F. M. Belpaire. Biotransformation of nitroglycerin by organic nitrate reductase. Arch. Int. Pharmacodyn. Ther. 196 Suppl 196:165 (1972).

    PubMed  Google Scholar 

  134. R. A. Okerholm, F. E. Peterson, F. J. Keeley, T. C. Smith, and A. J. Glazko. Bioavailability of norethindrone in human subjects. Eur. J. Clin. Pharmacol. 13:35–39 (1978).

    PubMed  CAS  Google Scholar 

  135. C. H. Verhoeven, T. T. van Munster, G. M. Groothuis, R. M. Vos, and I. M. Rietjens. Identification of the human P450 enzymes involved in the in vitro metabolism of the synthetic steroidal hormones Org 4060 and Org 30659. Xenobiotica. 32:109–118 (2002).

    PubMed  CAS  Google Scholar 

  136. W. Y. Kim, and L. Z. Benet. P-glycoprotein (P-gp/MDR1)-mediated efflux of sex-steroid hormones and modulation of P-gp expression in vitro. Pharm. Res. 21:1284–1293 (2004).

    PubMed  CAS  Google Scholar 

  137. W. G. Schoonen, G. H. Deckers, M. E. de Gooijer, R. de Ries, and H. J. Kloosterboer. Hormonal properties of norethisterone, 7alpha-methyl-norethisterone and their derivatives. J. Steroid. Biochem. Mol. Biol. 74:213–222 (2000).

    PubMed  CAS  Google Scholar 

  138. G. O. Kokwaro, and G. Taylor. Oxamniquine pharmacokinetics in healthy Kenyan African volunteers. East Afr. Med. J. 68:359–364 (1991).

    PubMed  CAS  Google Scholar 

  139. C. M. Masimirembwa, J. A. Hasler, and I. Johansson. Inhibitory effects of antiparasitic drugs on cytochrome P450 2D6. Eur. J. Clin. Pharmacol. 48:35–38 (1995).

    PubMed  CAS  Google Scholar 

  140. L. F. Prescott. Kinetics and metabolism of paracetamol and phenacetin. Br. J. Clin. Pharmacol. 10 Suppl 2:291S–298S (1980).

    PubMed  Google Scholar 

  141. J. Mohandas, G. G. Duggin, J. S. Horvath, and D. J. Tiller. Metabolic oxidation of acetaminophen (paracetamol) mediated by cytochrome P-450 mixed-function oxidase and prostaglandin endoperoxide synthetase in rabbit kidney. Toxicol. Appl. Pharmacol. 61:252–259 (1981).

    PubMed  CAS  Google Scholar 

  142. I. Manov, H. Motanis, I. Frumin, and T. C. Iancu. Hepatotoxicity of anti-inflammatory and analgesic drugs: ultrastructural aspects. Acta Pharmacol. Sin. 27:259–272 (2006).

    PubMed  CAS  Google Scholar 

  143. R. F. Bergstrom, D. R. Kay, T. M. Harkcom, and J. G. Wagner. Penicillamine kinetics in normal subjects. Clin. Pharmacol. Ther. 30:404–413 (1981).

    Article  PubMed  CAS  Google Scholar 

  144. P. Netter, B. Bannwarth, P. Pere, and A. Nicolas. Clinical pharmacokinetics of D-penicillamine. Clin. Pharmacokinet. 13:317–333 (1987).

    Article  PubMed  CAS  Google Scholar 

  145. A. E. Pilkington, and R. H. Waring. D-penicillamine metabolism: in vitro studies of S-oxidation mechanisms. Drug Metabol. Drug Interact. 6:85–93 (1988).

    PubMed  CAS  Google Scholar 

  146. C. Chen, and G. M. Pollack. Enhanced antinociception of the model opioid peptide [D-penicillamine] enkephalin by P-glycoprotein modulation. Pharm. Res. 16:296–301 (1999).

    PubMed  CAS  Google Scholar 

  147. J. Huwyler, M. B. Wright, H. Gutmann, and J. Drewe. Induction of cytochrome P450 3A4 and P-glycoprotein by the isoxazolyl-penicillin antibiotic flucloxacillin. Curr. Drug Metab. 7:119–126 (2006).

    PubMed  CAS  Google Scholar 

  148. N. Z. Nyazema, F. F. Mutamiri, I. Mudiwa, A. Chimuka, and J. Ndamba. Immunopharmacological aspects of praziquantel. Cent. Afr. J. Med. 41:284–288 (1995).

    PubMed  CAS  Google Scholar 

  149. S. Kaojarern, S. Nathakarnkikool, and U. Suvanakoot. Comparative bioavailability of praziquantel tablets. DICP. 23:29–32 (1989).

    PubMed  CAS  Google Scholar 

  150. W. Ridtitid, M. Wongnawa, W. Mahatthanatrakul, J. Punyo, and M. Sunbhanich. Rifampin markedly decreases plasma concentrations of praziquantel in healthy volunteers. Clin. Pharmacol. Ther. 72:505–513 (2002).

    PubMed  CAS  Google Scholar 

  151. R. Hayeshi, C. Masimirembwa, S. Mukanganyama, and A. L. Ungell. The potential inhibitory effect of antiparasitic drugs and natural products on P-glycoprotein mediated efflux. Eur. J. Pharm. Sci. 29:70–81 (2006).

    PubMed  CAS  Google Scholar 

  152. R. Preiss, F. Baumann, R. Regenthal, and M. Matthias. Plasma kinetics of procarbazine and azo-procarbazine in humans. Anticancer Drugs. 17:75–80 (2006).

    PubMed  CAS  Google Scholar 

  153. M. W. Coomes, and R. A. Prough. The mitochondrial metabolism of 1,2-disubstituted hydrazines, procarbazine and 1,2-dimethylhydrazine. Drug Metab. Dispos. 11:550–555 (1983).

    PubMed  CAS  Google Scholar 

  154. I. Bygbjerg, P. Ravn, A. Ronn, H. Flachs, and E. F. Hvidberg. Human pharmacokinetics of proguanil and its metabolites. Trop. Med. Parasitol. 38:77–80 (1987).

    PubMed  CAS  Google Scholar 

  155. E. M. Chiluba, K. A. Fletcher, and A. H. Price. The pharmacokinetics of proguanil in human subjects following a single oral dose. Afr. J. Med. Sci. 16:43–46 (1987).

    CAS  Google Scholar 

  156. N. A. Helsby, G. Edwards, A. M. Breckenridge, and S. A. Ward. The multiple dose pharmacokinetics of proguanil. Br. J. Clin. Pharmacol. 35:653–656 (1993).

    PubMed  CAS  Google Scholar 

  157. W. H. Hoffman, and J. N. Miceli. Pharmacokinetics of propylthiouracil in children and adolescents with Graves’ disease in the hyperthyroid and euthyroid states. Dev. Pharmacol. Ther. 11:73–81 (1988).

    PubMed  CAS  Google Scholar 

  158. H. Bjorn, D. R. Hennessy, and C. Friis. The kinetic disposition of pyrantel citrate and pamoate and their efficacy against pyrantel-resistant Oesophagostomum dentatum in pigs. Int. J. Parasitol. 26:1375–1380 (1996).

    PubMed  CAS  Google Scholar 

  159. G. E. Goodman, D. S. Alberts, Y. M. Peng, J. Beaudry, S. A. Leigh, and T. E. Moon. Plasma kinetics of oral retinol in cancer patients. Cancer Treat. Rep. 68:1125–1133 (1984).

    PubMed  CAS  Google Scholar 

  160. L. A. Hansen, C. C. Sigman, F. Andreola, S. A. Ross, G. J. Kelloff, and L. M. De Luca. Retinoids in chemoprevention and differentiation therapy. Carcinogenesis. 21:1271–1279 (2000).

    PubMed  CAS  Google Scholar 

  161. G. Acocella. Clinical pharmacokinetics of rifampicin. Clin. Pharmacokinet. 3:108–127 (1978).

    PubMed  CAS  Google Scholar 

  162. E. G. Schuetz, A. H. Schinkel, M. V. Relling, and J. D. Schuetz. P-glycoprotein: a major determinant of rifampicin-inducible expression of cytochrome P4503A in mice and humans. Proc. Natl. Acad. Sci. U. S. A. 93:4001–4005 (1996).

    PubMed  CAS  Google Scholar 

  163. D. A. Goldstein, Y. K. Tan, and S. J. Soldin. Pharmacokinetics and absolute bioavailability of salbutamol in healthy adult volunteers. Eur. J. Clin. Pharmacol. 32:631–634 (1987).

    PubMed  CAS  Google Scholar 

  164. D. J. Morgan, J. D. Paull, B. H. Richmond, E. Wilson-Evered, and S. P. Ziccone. Pharmacokinetics of intravenous and oral salbutamol and its sulphate conjugate. Br. J. Clin. Pharmacol. 22:587–593 (1986).

    PubMed  CAS  Google Scholar 

  165. S. Kaul, K. A. Dandekar, B. E. Schilling, and R. H. Barbhaiya. Toxicokinetics of 2′,3′-didehydro-3′-deoxythymidine, stavudine (D4T). Drug Metab. Dispos. 27:1–12 (1999).

    PubMed  CAS  Google Scholar 

  166. K. Z. Rana, and M. N. Dudley. Clinical pharmacokinetics of stavudine. Clin. Pharmacokinet. 33:276–284 (1997).

    PubMed  CAS  Google Scholar 

  167. S. L. Glynn, and M. Yazdanian. In vitro blood–brain barrier permeability of nevirapine compared to other HIV antiretroviral agents. J. Pharm. Sci. 87:306–310 (1998).

    PubMed  CAS  Google Scholar 

  168. E. M. Cretton, Z. Zhou, L. B. Kidd, H. M. McClure, S. Kaul, M. J. Hitchcock, and J. P. Sommadossi. In vitro and in vivo disposition and metabolism of 3′-deoxy-2′,3′-didehydrothymidine. Antimicrob. Agents Chemother. 37:1816–1825 (1993).

    PubMed  CAS  Google Scholar 

  169. H. R. Winter, and J. D. Unadkat. Identification of cytochrome P450 and arylamine N-acetyltransferase isoforms involved in sulfadiazine metabolism. Drug Metab. Dispos. 33:969–976 (2005).

    PubMed  CAS  Google Scholar 

  170. U. Klotz. Clinical pharmacokinetics of sulphasalazine, its metabolites and other prodrugs of 5-aminosalicylic acid. Clin. Pharmacokinet. 10:285–302 (1985).

    PubMed  CAS  Google Scholar 

  171. C. Beyeler, B. M. Frey, and H. A. Bird. Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br. J. Rheumatol. 36:54–58 (1997).

    PubMed  CAS  Google Scholar 

  172. C. M. Tallaksen, A. Sande, T. Bohmer, H. Bell, and J. Karlsen. Kinetics of thiamin and thiamin phosphate esters in human blood, plasma and urine after 50 mg intravenously or orally. Eur. J. Clin. Pharmacol. 44:73–78 (1993).

    PubMed  CAS  Google Scholar 

Download references

Acknowledgement

Akash Khandelwal and Praveen M. Bahadduri contributed equally to this work and should be considered co-first authors.

Author information

Author notes

  1. Cheng Chang

    Present address: Current address: Pfizer, Inc, Groton, Connecticut, USA

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Maryland, 20 Penn Street, Baltimore, Maryland, 21201, USA

    Akash Khandelwal, Praveen M. Bahadduri, Cheng Chang, James E. Polli, Peter W. Swaan & Sean Ekins

  2. ACT LLC, 601 Runnymede Avenue, Jenkintown, Pennsylvania, 19046, USA

    Sean Ekins

Authors
  1. Akash Khandelwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Praveen M. Bahadduri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cheng Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. James E. Polli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peter W. Swaan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sean Ekins
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter W. Swaan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khandelwal, A., Bahadduri, P.M., Chang, C. et al. Computational Models to Assign Biopharmaceutics Drug Disposition Classification from Molecular Structure. Pharm Res 24, 2249–2262 (2007). https://doi.org/10.1007/s11095-007-9435-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-007-9435-9

Key words

Search

Navigation