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Lack of a pharmacokinetic drug-drug interaction with venlafaxine extended-release/indinavir and desvenlafaxine extended-release/indinavir

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To assess the effects of venlafaxine extended-release (XR) capsules and desvenlafaxine extended-release (XR) tablets upon indinavir pharmacokinetic properties when co-administrated to healthy volunteers.

Methods

This was an open-label, two-period, fixed-dose study conducted at the clinical research unit located on a university campus. Twenty-four healthy volunteers enrolled in the study (mean age 28.3 ± 8.0 years).

Each subject received a single dose of indinavir 800 mg on day 1. Subsequently, subjects were then randomly assigned to either the venlafaxine XR group (N = 12) or the desvenlafaxine XR group (N = 12). Starting on day 2, venlafaxine XR was dosed at 37.5 mg/day for 4 days and increased to 75 mg/day for 6 days. Desvenlafaxine XR was dosed at 50 mg/day for 10 days. On day 12, indivanvir 800 mg was co-administered to both the venlafaxine XR and the desvenlafaxine XR groups. The pharmacokinetics of indinavir were determined both before and at the end of antidepressant dosing. Plasma indinavir, venlafaxine, and desvenlafaxine concentrations were assayed by high-performance liquid chromatography with ultra-violet (UV) detection. Indinavir pharmacokinetic parameters were calculated by noncompartmental analysis using validated computer software.

Results

Venlafaxine XR and desvenlafaxine XR did not produce any significant changes in indinavir disposition. Both antidepressants were well tolerated by the subjects with only minor adverse side effects.

Conclusions

No pharmacokinetic drug-drug interaction was demonstrated between venlafaxine XR and indinavir or between desvenlafaxine XR and indinvair. The lack of interaction could be due to the venlafaxine and desvenlafaxine extended-release formulation.

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References

  1. Center for Disease Control and Prevention (2008) HIV prevalence estimates—United States, 2006. Morb Mortal Wkly Rep 57:1073–1076

    Google Scholar 

  2. Joint United Nations Programme on HIV/AIDS (2009) AIDS epidemic update 2009. http://www.unaids.org/en/KnowledgeCentre/HIVData/EpiUpdate/EpiUpdArchive/2009/default.aso. Accessed October 28, 2010

  3. Penzak SR, Reddy YS, Grimsley SR (2000) Depression in patients with HIV infection. Am J Health-System Pharm 57:376–389

    CAS  Google Scholar 

  4. Rabkin JG (2008) HIV and depression: 2008 review and update. Current HIV/AIS Rep 25:163–171

    Article  Google Scholar 

  5. Thompson MA, Aberg JA, Cahn P, Montaner JS et al (2010) International AIDS Society-USA. Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society—USA panel. JAMA 304:321–333

    Article  PubMed  CAS  Google Scholar 

  6. Otton SV, Ball SE, Cheung SW, Inaba T, Rupdolph RL, Sellers EM (1996) Venlafaxine oxidation in vitro is catalyzed by CYP2D6. Br J Clin Pharmacol 41:149–156

    Article  PubMed  CAS  Google Scholar 

  7. Ball SE, Ahert D, Scatina J, Kao J (1997) Venlafaxine: in vitro inhibition of CYP2D6 dependent imipramine metabolism; comparative studies with selected SSRIs and effect on human hepatic CYP3A4, CYP2C9, and CYP1A2. Br J Clin Pharmacol 43:619–626

    Article  PubMed  CAS  Google Scholar 

  8. Oganesian A, Shilling AD, Young-Sciame R, Tran J, Watanyar A, Azam F, Kao J, Leung L (2009) Desvenlafaxine and venlafaxine exert minimal in vitro inhibition of human cytochrome P450 and P-glycoprotein activities. Psychopharm Bull 42:1–17

    Google Scholar 

  9. Levin GL, Nelson LA, DeVane CL, Preston SL, Eisle G, Carson SW (2001) A pharmacokinetic drug-drug interaction study of venlafaxine and indinavir. Psychopharm Bull 35:62–71

    CAS  Google Scholar 

  10. Kim RB, Fromm MF, Wandel C, Leake B, Wood AJJ, Roden DM, Wilkinson GR (1998) The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest 101:289–294

    Article  PubMed  CAS  Google Scholar 

  11. Hochman JH, Chiba M, Yamazaki M, Lin JH (2000) Influence of P-glycoprotein on the transport and metabolism on indinavir in caco-2 cells expressing cytochrome P-450 3A4. J Pharmacol Exp Ther 292:292–318

    Google Scholar 

  12. Von Moltke LL, Duan SX, Greenblatt DJ, Fogelman SM, Schmider J, Harmatz JS, Shader RI (1997) Venlafaxine and metabolites are very weak inhibitors of human cytochrome P450-3A isoforms. Biol Psychiatry 41:377–380

    Article  Google Scholar 

  13. Karlsson L, Schmitt U, Josefsson M, Carlson B, Ahlner J, Bengtsson F, Kugelberg FC, Hiemke C (2010) Blood–brain barrier penetration of the enantiomers of venlafaxine and its metabolites in mice lacking P-glycoprotein. Eur Neuropsychopharmacol 20:632–640

    Article  PubMed  CAS  Google Scholar 

  14. Bachman CJ, Beauleiu-Abdelahad D, Ganey NJ, Mullan MJ, Levin GM (2011) Induction of drug efflux protein expression by venlafaxine but not desvenlafaxine. Biopharm Drug Disposition 32:233–234

    Article  Google Scholar 

  15. Yu DK (1999) The contribution of P-glycoprotein to pharmacokinetic drug-drug interactions. J Clin Pharmacol 39:1203–1211

    Article  PubMed  CAS  Google Scholar 

  16. Zhou SF (2008) Structure, function, and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica 38:802–812

    Article  PubMed  CAS  Google Scholar 

  17. Aller SG, Yu J, Ward A, Weng Y et al (2009) Structure of P-glycoprotein reveals a molecular basis of poly-specific drug binding. Science 323:1718–1722

    Article  PubMed  CAS  Google Scholar 

  18. Stolley PD, Strom BL (1986) Sample size calculation for clinical pharmacology studies. Clin Pharmacol Ther 39:489–490

    Article  PubMed  CAS  Google Scholar 

  19. Penzak SR, Acosta EP, Truner M, Edwards DJ, Hon YY, Desai HD, Jann MW (2002) Effect of Seville orange juice and grapefruit juice on indinavir pharmacokinetics. J Clin Pharmcol 42:1165–1170

    Article  CAS  Google Scholar 

  20. Carver PL, Fleisher D, Zhou SY, Kaul D, Kazanjian P, Li C (1999) Meal composition effects of the oral bioavailability of indinavir in HIV-infectd patients. Pharm Res 16:718–724

    Article  PubMed  CAS  Google Scholar 

  21. Shelton MJ, Wynn HE, Hewitt RG, DiFrancesco R (2001) Effects of grapefruit juice in pharmacokinetic exposure to indinavir in HIV-positive patients. J Clin Pharmacol 41:435–442

    Article  PubMed  CAS  Google Scholar 

  22. Sopko MA, Ehret MJ, Grgas M (2008) Desvenlafaxine: another “me too” drug? Ann Pharmacotherapy 42:1439–1446

    Article  CAS  Google Scholar 

  23. Filho JH, Bonifacio FN, Bedor DCG et al (2010) Relative bioavailability of two formulations of venlafaxine extended-release 75 mg capsules in healthy Brazilian male volunteers: a single-dose, randomized sequence, open-label, two-period crossover study in fasting and fed states. Clin Ther 32:2088–2096

    Article  Google Scholar 

  24. Zhang Y, Benet LZ (2001) The gut as a barrier to drug absorption. Clin Pharmacokinet 40:159–168

    Article  PubMed  CAS  Google Scholar 

  25. Penzak SR (2005) Mechanism of drug interactions 2: transport proteins. In: Piscitelli SC, Rodvold KA (eds) Drug interactions in infectious disease, 2nd edn. Humana, Totowa, NJ, pp 41–82

    Chapter  Google Scholar 

  26. Saradhi M, Kumar N, Reddy RC, Tyagi RK (2006) Pregane and xenobiotic receptor (PXR): a promiscuous xenosensor in human health and disease. J Endocrinol Reproduct 10:1–12

    Google Scholar 

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Competing interests

This study was supported by Pfizer, Inc. through the investigator-initiated research study program. Dr. Jann has received research grants from Pfizer and Janssen Pharmaceuticals. Drs. Spratlin and VanDenBerg have received research grants from Pfizer, Johnson/Johnson, Eli Lilly, and the Coca Cola Company. Dr. Momary has received research funding from Pfizer. Dr. Zhang, Dr. Penzak, Dr. Wright, and Mr. Turner have nothing to disclose.

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Authors and Affiliations

  1. Mercer University College of Pharmacy and Health Sciences, 3001 Mercer University Dr., Atlanta, GA, 30341, USA

    Michael W. Jann, Vicky Spratlin, Kathryn Momary, Hailing Zhang, David Turner, Alan Wright & Chad VanDenBerg

  2. Clinical Pharmacokinetics Laboratory, National Institutes of Health, Bethesda, MD, USA

    Scott R. Penzak

Authors
  1. Michael W. Jann
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  2. Vicky Spratlin
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  3. Kathryn Momary
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  4. Hailing Zhang
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  5. David Turner
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  6. Scott R. Penzak
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  7. Alan Wright
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  8. Chad VanDenBerg
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Correspondence to Michael W. Jann.

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Jann, M.W., Spratlin, V., Momary, K. et al. Lack of a pharmacokinetic drug-drug interaction with venlafaxine extended-release/indinavir and desvenlafaxine extended-release/indinavir. Eur J Clin Pharmacol 68, 715–721 (2012). https://doi.org/10.1007/s00228-011-1180-7

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  • DOI: https://doi.org/10.1007/s00228-011-1180-7

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