The pharmacokinetics and pharmacodynamics of atovaquone and proguanil for the treatment of uncomplicated falciparum malaria in third-trimester pregnant women

Abstract

The pharmacokinetics of atovaquone and cycloguanil appeared to be influenced by the pregnancy status, resulting in an decrease in the Cmax and AUC of approximately twofold.

Intermittent preventive treatment for malaria in pregnancy in Africa: What's new, what's needed?

“…Late pregnancy and use of oral contraceptives impair formation of the active metabolite, probably due to inhibition of the metabolizing isoenzyme as a result of elevated oestrogen levels[80]. The pharmacokinetics of proguanil and cycloguanil are significantly altered in pregnant women with malaria compared to healthy volunteers and children with uncomplicated falciparum malaria[81]…”

Spezifische pharmakodynamische Interaktion zwischen Atovaquon und Retinol bei Plasmodium falciparum

“…Reversely, the lower the sensitivity to atovaquone, the higher will be the enhancing effect of retinol. This was particularly evi- In all cases, the EC99 values (or minimum effective concentrations, MIC) for atovaquone observed with ATO-RET medium and ATO-RET high were below the lowest atovaquone peak plasma concentration (3625 nM) observed in a clinical trial of Malarone ® in pregnant women whose peak plasma concentrations and AUC values are about half of those observed in non-pregnant individuals [28]. Therefore the enhancing effect of retinol is probably highest where it is needed most, namely in parasites with an intrinsically low sensitivity to atovaquone.…”

“…Inter-isolate specific sensitivity of P. falciparum to atovaquone spans a relatively wide range. So do the peak concentrations and concentration-time profiles (AUC) of atovaquone [28], a sign of widely varying absorption from the intestinal tract.…”

Embryotoxicity of artesunate in animal species related to drug tissue distribution and toxicokinetic profiles

“…There are a number of studies that have been published on the oral treatment of pregnant and non-pregnant women with both artemisinins and other antimalarials, including studies of chloroquine (Fakeye et al, 2002;Massele et al, 1997), mefloquine (Na- Bangchang et al, 1994), proguanil (McGready et al, 2003aNa-Bangchang et al, 2005), atovaquone (McGready et al, 2003a,b), and DHA . All of these studies reveal altered kinetics in pregnancy, with plasma levels significantly lower in pregnant than in non-pregnant patients with malaria (Dawes and Chowienczyk, 2001;Ward et al, 2007).…”