Minzi O.M.S., Gupta A., Haule A.F., Kagashe G.A.B., Massele A.Y., Gustafsson L.L.
Department of Medicinal Chemistry, School of Pharmacy, Muhimbili University College of Health Sciences, P.O. Box 65013, Dar es Salaam, Tanzania; Shelys Pharmaceutical Limited, P.O. BOX 3016, Dar es Salaam, Tanzania; Department of Pharmaceutics and Pharmaceutical Microbiology, School of Pharmacy, Muhimbili University College of Health Sciences, P.O. Box 65013, Dar es Salaam, Tanzania; Department of Clinical Pharmacology, School of Medicine, Muhimbili University College of Health Sciences, P.O. Box 65010, Dar es Salaam, Tanzania; Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institute, 41 86, Huddinge, Stockholm, Sweden
Minzi, O.M.S., Department of Medicinal Chemistry, School of Pharmacy, Muhimbili University College of Health Sciences, P.O. Box 65013, Dar es Salaam, Tanzania; Gupta, A., Shelys Pharmaceutical Limited, P.O. BOX 3016, Dar es Salaam, Tanzania; Haule, A.F., Department of Medicinal Chemistry, School of Pharmacy, Muhimbili University College of Health Sciences, P.O. Box 65013, Dar es Salaam, Tanzania; Kagashe, G.A.B., Department of Pharmaceutics and Pharmaceutical Microbiology, School of Pharmacy, Muhimbili University College of Health Sciences, P.O. Box 65013, Dar es Salaam, Tanzania; Massele, A.Y., Department of Clinical Pharmacology, School of Medicine, Muhimbili University College of Health Sciences, P.O. Box 65010, Dar es Salaam, Tanzania; Gustafsson, L.L., Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institute, 41 86, Huddinge, Stockholm, Sweden
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 C max), time required to attain peak concentration (Tmax), half-life (t 1/2) 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 1/2 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 1/2 between the two arms (p>0.05). Conclusion Taking AT concomitantly with SP does not have any impact in the disposition of SP. © 2007 Springer-Verlag.
artesunate; fansidar; adult; article; blood analysis; blood sampling; clinical trial; controlled clinical trial; controlled study; crossover procedure; drug distribution; drug half life; high performance liquid chromatography; human; male; normal human; priority journal; randomized controlled trial; room temperature; tablet; Adult; Antimalarials; Area Under Curve; Artemisinins; Chromatography, High Pressure Liquid; Cross-Over Studies; Drug Combinations; Drug Interactions; Half-Life; Humans; Malaria, Falciparum; Pyrimethamine; Sesquiterpenes; Sulfadoxine