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dc.contributor.authorAbd-Rahman, AN
dc.contributor.authorMarquart, L
dc.contributor.authorGobeau, N
dc.contributor.authorKummel, A
dc.contributor.authorSimpson, JA
dc.contributor.authorChalon, S
dc.contributor.authorMohrle, JJ
dc.contributor.authorMcCarthy, JS
dc.date.accessioned2020-11-27T00:24:32Z
dc.date.available2020-11-27T00:24:32Z
dc.date.issued2020-07-02
dc.identifier.citationAbd-Rahman, A. N., Marquart, L., Gobeau, N., Kummel, A., Simpson, J. A., Chalon, S., Mohrle, J. J. & McCarthy, J. S. (2020). Population Pharmacokinetics and Pharmacodynamics of Chloroquine in aPlasmodium vivaxVolunteer Infection Study. CLINICAL PHARMACOLOGY & THERAPEUTICS, 108 (5), pp.1055-1066. https://doi.org/10.1002/cpt.1893.
dc.identifier.issn0009-9236
dc.identifier.urihttp://hdl.handle.net/11343/252451
dc.description.abstractChloroquine 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-1 (95% CI 0.196-0.230), translating to a parasite clearance half-life of 4.5 hours (95% CI 4.1-5.0) and a parasite reduction ratio of 400 every 48 hours (95% CI 320-500). This is the first study that characterized the PK/PD relationship between chloroquine plasma and whole blood concentrations and P. vivax clearance using a semimechanistic population PK/PD modeling. This PK/PD model can be used to optimize dosing scenarios and to identify optimal dosing regimens for chloroquine where resistance to chloroquine is increasing.
dc.languageEnglish
dc.publisherWILEY
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titlePopulation Pharmacokinetics and Pharmacodynamics of Chloroquine in aPlasmodium vivaxVolunteer Infection Study
dc.typeJournal Article
dc.identifier.doi10.1002/cpt.1893
melbourne.affiliation.departmentMelbourne School of Population and Global Health
melbourne.source.titleClinical Pharmacology and Therapeutics
melbourne.source.volume108
melbourne.source.issue5
melbourne.source.pages1055-1066
dc.rights.licensecc-by
melbourne.elementsid1453703
melbourne.contributor.authorSimpson, Julie
dc.identifier.eissn1532-6535
melbourne.accessrightsOpen Access


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