Publication: Population pharmacokinetic and pharmacodynamic modeling of amodiaquine and desethylamodiaquine in women with Plasmodium vivax Malaria during and after pregnancy
Issued Date
2012-11-01
Resource Type
ISSN
10986596
00664804
00664804
Other identifier(s)
2-s2.0-84868016736
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.56, No.11 (2012), 5764-5773
Suggested Citation
Joel Tarning, Palang Chotsiri, Vincent Jullien, Marcus J. Rijken, Martin Bergstrand, Mireille Cammas, Rose McGready, Pratap Singhasivanon, Nicholas P J Day, Nicholas J. White, Francois Nosten, Niklas Lindegardh Population pharmacokinetic and pharmacodynamic modeling of amodiaquine and desethylamodiaquine in women with Plasmodium vivax Malaria during and after pregnancy. Antimicrobial Agents and Chemotherapy. Vol.56, No.11 (2012), 5764-5773. doi:10.1128/AAC.01242-12 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/14584
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Population pharmacokinetic and pharmacodynamic modeling of amodiaquine and desethylamodiaquine in women with Plasmodium vivax Malaria during and after pregnancy
Abstract
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 mixedeffects 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. Copyright © 2012, American Society for Microbiology. All Rights Reserved.