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Lack of impact of artesunate on the disposition kinetics of sulfadoxine/pyrimethamine when the two drugs are concomitantly administered

  • Pharmacokinetics and Disposition
  • Published:
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Abstract

Objective

To determine the effect of artesunate (AT) on the disposition kinetics of sulfadoxine/pyrimethamine (SP) in humans.

Methods

In a randomized cross-over study, 16 healthy volunteers were given a dose of three SP tablets containing 500 mg of sulfadoxine (SDX) and 25 mg of pyrimethamine (PYR) (=SP group), while the second arm received three SP tablets + two AT tablets of 200 mg in total followed by 100 mg AT for the next 4 days (SP+AT group). Blood samples (100 μl) were collected by means of a finger prick and dried on filter paper. The blood spots were wrapped in polythene folders and stored at room temperature until analysis. The samples were assayed using high-performance liquid chromatographic methods.

Results

The peak concentration Cmax), time required to attain peak concentration (Tmax), half-life (t ½) and area under the plasma concentration-time curve (AUC) were determined. The Cmax of SDX were 92.9 and 98.9 μg/ml for the SP and SP+AT arms, respectively; for PYR, these were 0.86 and 0.79 μg/ml, respectively. The Tmax of SDX were 10 and 8 h for the SP and SP+AT arms, respectively; for PYR, these were 4.0 and 3.0 h, respectively. The AUC0–288 of SDX were 15,840 and 18,876 μg/ml h for the SP and SP+AT arms, respectively; for PYR, they were 124 and 112 μg/ml h, respectively. The t ½ of values for SDX were 165 and 180 h for the SP and SP+AT arms, respectively; for PYR, these were 158 and 177 h, respectively. There was no statistically significant difference between the Cmax, Tmax, AUC0–288 and t ½ between the two arms (p > 0.05).

Conclusion

Taking AT concomitantly with SP does not have any impact in the disposition of SP.

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Acknowledgements

This study was financially supported by the Swedish Agency for Research Cooperation with Developing Countries (SAREC), through grant no. SWE-2000-175, SWE-BIL-96, and is gratefully acknowledged. The Sumaria Group Ltd in Tanzania also provided additional funding for the study. Mr. Bwile Paschal ran the HPLC sample analyses whereas Dr. Mary Jande, Mr. Jumanne Mng’agi, Mr. James Fulgence and Mr. Walter Msangi gave technical support. The Division of Clinical Pharmacology at Kalorinska Institute in Stockholm., donated the pharmacokinetic software. This study would not have been possible without the participation of volunteers. We highly thank them for committing their time and willingness to participate in the study.

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Authors and Affiliations

  1. Department of Medicinal Chemistry, School of Pharmacy, Muhimbili University College of Health Sciences, P.O. Box 65013, Dar es Salaam, Tanzania

    O. M. S. Minzi & A. F. Haule

  2. Shelys Pharmaceutical Limited, P.O. BOX 3016, Dar es Salaam, Tanzania

    A. Gupta

  3. Department of Pharmaceutics and Pharmaceutical Microbiology, School of Pharmacy, Muhimbili University College of Health Sciences, P.O. Box 65013, Dar es Salaam, Tanzania

    G. A. B. Kagashe

  4. Department of Clinical Pharmacology, School of Medicine, Muhimbili University College of Health Sciences, P.O. Box 65010, Dar es Salaam, Tanzania

    A. Y. Massele

  5. Unit of Tropical Pharmacology, Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institute, 41 86, Huddinge, Stockholm, Sweden

    L. L. Gustafsson

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  1. O. M. S. Minzi
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  2. A. Gupta
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Correspondence to O. M. S. Minzi.

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Minzi, O.M.S., Gupta, A., Haule, A.F. et al. Lack of impact of artesunate on the disposition kinetics of sulfadoxine/pyrimethamine when the two drugs are concomitantly administered. Eur J Clin Pharmacol 63, 457–462 (2007). https://doi.org/10.1007/s00228-007-0278-4

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  • DOI: https://doi.org/10.1007/s00228-007-0278-4

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