Population Pharmacokinetics and Pharmacodynamics of Chloroquine in a Plasmodium vivax Volunteer Infection Study.
Administration, Oral
Adult
Antimalarials
/ administration & dosage
Biotransformation
Chloroquine
/ administration & dosage
Drug Dosage Calculations
Drug Resistance
Female
Humans
Malaria, Vivax
/ blood
Male
Models, Biological
Parasite Load
Plasmodium vivax
/ drug effects
Treatment Outcome
Young Adult
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
11
03
2020
accepted:
07
05
2020
pubmed:
18
5
2020
medline:
26
5
2021
entrez:
17
5
2020
Statut:
ppublish
Résumé
Chloroquine has been used for the treatment of malaria for > 70 years; however, chloroquine pharmacokinetic (PK) and pharmacodynamic (PD) profile in Plasmodium vivax malaria is poorly understood. The objective of this study was to describe the PK/PD relationship of chloroquine and its major metabolite, desethylchloroquine, in a P. vivax volunteer infection study. We analyzed data from 24 healthy subjects who were inoculated with blood-stage P. vivax malaria and administered a standard treatment course of chloroquine. The PK of chloroquine and desethylchloroquine was described by a two-compartment model with first-order absorption and elimination. The relationship between plasma and whole blood concentrations of chloroquine and P. vivax parasitemia was characterized by a PK/PD delayed response model, where the equilibration half-lives were 32.7 hours (95% confidence interval (CI) 27.4-40.5) for plasma data and 24.1 hours (95% CI 19.0-32.7) for whole blood data. The estimated parasite multiplication rate was 17 folds per 48 hours (95% CI 14-20) and maximum parasite killing rate by chloroquine was 0.213 hour
Identifiants
pubmed: 32415986
doi: 10.1002/cpt.1893
pmc: PMC7276750
doi:
Substances chimiques
Antimalarials
0
Chloroquine
886U3H6UFF
desethylchloroquine
ZC9Z9XX2PD
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1055-1066Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
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