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Eur J Clin Pharmacol. 2009 Aug;65(8):809-21. doi: 10.1007/s00228-009-0656-1. Epub 2009 Apr 30.

Tolerability and pharmacokinetics of non-fixed and fixed combinations of artesunate and amodiaquine in Malaysian healthy normal volunteers.

Author information

1
National Center for Drug Research (CRD), Universiti Sains Malaysia (USM), 11800 Minden, Pulau Pinang, Penang, Malaysia.

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 2x2 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 C(max) were compared by an analysis of variance (ANOVA) based on geometric least square means using the Schuirmann two one-sided test.

RESULTS:

The AUC(0-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.

PMID:
19404632
PMCID:
PMC2714898
DOI:
10.1007/s00228-009-0656-1
[Indexed for MEDLINE]
Free PMC Article

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