Tolerability and pharmacokinetics of non-fixed and fixed combinations of artesunate and amodiaquine in Malaysian healthy normal volunteers
Open Access
- 30 April 2009
- journal article
- research article
- Published by Springer Nature in European Journal of Clinical Pharmacology
- Vol. 65 (8), 809-821
- https://doi.org/10.1007/s00228-009-0656-1
Abstract
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. 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. 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. Both combinations were well tolerated and had comparable pharmacokinetic profiles; differences are unlikely to be clinically relevant.Keywords
This publication has 24 references indexed in Scilit:
- Dosing accuracy of artesunate and amodiaquine as treatment for falciparum malaria in Casamance, SenegalTropical Medicine & International Health, 2009
- Evidence of Artemisinin-Resistant Malaria in Western CambodiaNew England Journal of Medicine, 2008
- Pharmacokinetics and tolerability of artesunate and amodiaquine alone and in combination in healthy volunteersEuropean Journal of Clinical Pharmacology, 2008
- Efficacy and safety of artesunate plus amodiaquine in routine use for the treatment of uncomplicated malaria in Casamance, southern SénégalMalaria Journal, 2007
- Plasmodium falciparum -Based Bioassay for Measurement of Artemisinin Derivatives in Plasma or SerumAntimicrobial Agents and Chemotherapy, 2004
- Comparison of Oral Artesunate and Dihydroartemisinin Antimalarial Bioavailabilities in Acute Falciparum MalariaAntimicrobial Agents and Chemotherapy, 2002
- Oral Artesunate Dose-Response Relationship in Acute Falciparum MalariaAntimicrobial Agents and Chemotherapy, 2002
- A comparison of oral artesunate and artemether antimalarial bioactivities in acute falciparum malariaBritish Journal of Clinical Pharmacology, 2001
- Acute asymptomatic hepatitis in a healthy normal volunteer exposed to 2 oral doses of amodiaquine and artesunateTransactions of the Royal Society of Tropical Medicine and Hygiene, 2001
- Strategies for the prevention of antimalarial drug resistance: Rationale for combination chemotherapy for malariaParasitology Today, 1996