Abstract
Objective: There is limited pharmacokinetic data available for the combination artesunate + amodiaquine, which is used widely to treat uncomplicated malaria. This study examines the bioavailability and tolerability of a fixed (200 mg artesunate + 540 mg amodiaquine) and loose (200 mg∈+∈612 mg) combination with a 2×2 cross-over design in 24 healthy volunteers. Methods: Parent compounds and metabolites [dihydroartemisinin (DHA) and desethylamodiaquine (DEAQ)] were measured by high-performance liquid chromatography-electrochemical detection, and the area under the curve (AUC)0-t and Cmax were compared by an analysis of variance (ANOVA) based on geometric least square means using the Schuirmann two one-sided test. Results: The AUC0-t for total DHA and DEAQ were 1522 ± 633 and 30021 ± 14211 ng h/ml for the fixed products and 1688 ± 767 and 40261 ± 19824 ng h/ml (mean ± standard deviation) for the loose products. The ANOVA showed no statistical differences except for sequence effect for DHA. The values obtained with the fixed product were within the 125% bioequivalent limits but extend below the 80% bioequivalence limits. Conclusion: Both combinations were well tolerated and had comparable pharmacokinetic profiles; differences are unlikely to be clinically relevant.
Original language | English |
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Pages (from-to) | 809-821 |
Number of pages | 13 |
Journal | European Journal of Clinical Pharmacology |
Volume | 65 |
Issue number | 8 |
DOIs | |
Publication status | Published - Aug 2009 |
Keywords
- Amodiaquine
- Artesunate
- Fixed combination treatment
- Non-fixed combination treatment
- Pharmacokinetics
- Tolerability