Amodiaquine is effective for the treatment of
Plasmodium vivax malaria, but there is little information on the pharmacokinetic and pharmacodynamic properties of
amodiaquine in pregnant women with
malaria. This study evaluated the population pharmacokinetic and pharmacodynamic properties of
amodiaquine and its biologically active metabolite,
desethylamodiaquine, in pregnant women with P. vivax
infection and again after delivery. Twenty-seven pregnant women infected with P.
vivax malaria on the Thai-Myanmar border were treated with
amodiaquine monotherapy (10 mg/kg/day) once daily for 3 days. Nineteen women, with and without P. vivax
infections, returned to receive the same
amodiaquine dose postpartum. Nonlinear mixed-effects modeling was used to evaluate the population pharmacokinetic and pharmacodynamic properties of
amodiaquine and
desethylamodiaquine.
Amodiaquine plasma concentrations were described accurately by lagged first-order absorption with a two-compartment disposition model followed by a three-compartment disposition of
desethylamodiaquine under the assumption of complete in vivo conversion.
Body weight was implemented as an allometric function on all clearance and volume parameters.
Amodiaquine clearance decreased linearly with age, and absorption lag time was reduced in pregnant patients. Recurrent
malaria infections in pregnant women were modeled with a time-to-event model consisting of a constant-hazard function with an inhibitory effect of
desethylamodiaquine.
Amodiaquine treatment reduced the risk of
recurrent infections from 22.2% to 7.4% at day 35. In conclusion, pregnancy did not have a clinically relevant impact on the pharmacokinetic properties of
amodiaquine or
desethylamodiaquine. No dose adjustments are required in pregnancy.