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Cited by 51Malaria Research and ControlPharmaceutical studies and practicesPharmacogenetics and Drug Metabolism

Population Pharmacokinetic and Pharmacodynamic Modeling of Amodiaquine and Desethylamodiaquine in Women with Plasmodium vivax Malaria during and after Pregnancy

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Tarning, Joel, Chotsiri, Palang, Jullien, Vincent, Rijken, Marcus J., Bergstrand, Martin, Cammas, Mireille, McGready, Rose, Singhasivanon, Pratap +4 more·2012·Antimicrobial Agents and Chemotherapy
DOI 10.1128/aac.01242-12PMC PMC3486620
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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 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.

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Crossref · 10.1128/aac.01242-12

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  • A pharmacokinetics study on AQ for treatment of P. vivax in pregnancy conducted in Thailand indicates the doses are similar to that of non-pregnant adults.

    “A pharmacokinetics study on AQ for treatment of P.vivax in pregnancy conducted in Thailand indicates the doses are similar to that of non-pregnant adults.131,135”

    From Malaria in pregnancy. (2013) · cites this paper as [135]

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Authors
Tarning, J., Chotsiri, P., Jullien, V., Rijken, M. J., Bergstrand, M., Cammas, M., McGready, R., Singhasivanon, P., Day, N. P. J., White, N. J., Nosten, F., & Lindegardh, N.
Affiliations
  • Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
  • Mahidol University (TH)
  • Inserm (FR)
  • Shoklo Malaria Research Unit (TH)
  • Uppsala University (SE)
ORCID
Venue
Antimicrobial Agents and Chemotherapy
Publisher
American Society for Microbiology
Published
2012-11
Volume
56
Issue
11
Pages
5764-5773
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
DOI
10.1128/aac.01242-12
PMC
PMC3486620
OpenAlex
W2135660833
Cited by
51
References
5
Citations by year
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FWCI
4.95
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Antimicrobial Agents and Chemotherapy (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Bill and Melinda Gates Foundation
  • Northwestern University
  • Wellcome Trust (089275, 093956, 093956/Z/10/Z)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
amodiaquine, desethylamodiaquine, vivax malaria, pregnancy, pharmacokinetics, pharmacodynamics, drug metabolism in pregnancy, recurrent malaria, dose adjustment, allometric scaling, nonlinear mixed-effects models
MeSH terms
Adolescent, Adult, Amodiaquine, Antimalarials, Biotransformation, Body Weight, Drug Administration Schedule, Female, Humans, Plasmodium vivax, Pregnancy, Pregnancy Complications, Parasitic, Malaria, Vivax, Nonlinear Dynamics, Secondary Prevention

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