2010 - Berlin - Germany

PAGE 2010: Applications- Anti-infectives
Joel Tarning

Population pharmacokinetics of antimalarial drugs in the treatment of pregnant women with uncomplicated malaria

J. Tarning(1,2), R. Hoglund(3), P. Chotsiri(1), W. Hanpithakpong(1), A.P. Pyo(4), V. Jullien(5), N. Lindegardh(1,2), M. Rijken(4), I. Adam(6), F. Nosten(1,2,4)

(1)Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand; (2)CCVTM, Churchill Hospital, Oxford, UK; (3)Department of Pharmacology, University of Gothenburg, Goteborg, Sweden; (4)Shoklo Malaria Research Unit, Mae Sot, Thailand; (5)Service de Pharmacologie Clinique, Groupe Hospitalier Cochin-Saint-Vincent de Paul, Paris, France; (6)Faculty of Medicine, University of Khartoum, Khartoum, Sudan

Objectives: Pregnancy has considerable effects on the pharmacokinetic properties of many of the drugs used to treat uncomplicated falciparum malaria. Several studies have shown reduced antimalarial drug concentrations in later pregnancy. Unfortunately, pregnant women are especially vulnerable to malaria and the fetus is adversely affected. No reports have described the pharmacokinetic properties of piperaquine, amodiaquine or desethylamodiaquine in pregnant women with uncomplicated malaria.

Methods: A pharmacokinetic study were conducted in Thailand (24 pregnant and 24 non-pregnant women) and in Sudan (12 pregnant and 14 non-pregnant women). These studies investigated the pharmacokinetic properties of piperaquine after a standard oral three-day fixed dose regimen of dihydroartemisinin-piperaquine in patients with uncomplicated falciparum malaria. Pharmacokinetics of amodiaquine and its principal biologically active metabolite desethylamodiaquine was investigated in the treatment of vivax infections in 28 pregnant women during pregnancy and again after delivery. Dense venous plasma samples were collected and drug measurements conducted according to published methods. Concentration-time profiles were characterized using NONMEM. Different structural models and the impact of different covariates on pharmacokinetic parameters were investigated in full for all three antimalarials.

Results & Conclusions: Population pharmacokinetics of piperaquine, amodiaquine and desethylamodiaquine was accurately described using a population pharmacokinetic modeling approach and results were compared with available literature for a full understanding of potential pregnancy related changes on pharmacokinetics and the impact of these on the pharmacodynamics.

Reference: PAGE 19 (2010) Abstr 1878 [www.page-meeting.org/?abstract=1878]
Poster: Applications- Anti-infectives