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Pharmacokinetics of Hydroxychloroquine and Its Clinical Implications in Chemoprophylaxis against Malaria Caused by Plasmodium vivax

Cited 73 time in Web of Science Cited 77 time in Scopus
Authors
Lim, Hyeong-Seok; Im, Jeong-Soo; Cho, Joo-Youn; Bae, Kyun-Seop; Yeom, Joon-Sup; Choi, Jae-Seon; Park, Jae-Won; Jang, In-Jin; Kim, Tae-Seon; Klein, Terry A.
Issue Date
2009-04
Publisher
AMER SOC MICROBIOLOGY
Citation
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY; Vol.53 4; 1468-1475
Abstract
Hydroxychloroquine (HCQ) is an antimalarial drug used as chemoprophylaxis against malaria caused by Plasmodium vivax in the Republic of Korea Army (ROKA). In this study, we evaluated the pharmacokinetics (PK) of HCQ and its metabolites and the relationship between the PK of HCQ and the effect of treatment of HCQ on vivax malaria in South Koreans. Three PK studies of HCQ were conducted with 91 healthy subjects and patients with vivax malaria. Plasma concentrations were analyzed by noncompartmental and mixed-effect modeling approaches. A two-compartment model with first-order absorption best described the data. The clearance and the central and peripheral volumes of distribution were 15.5 liters/h, 733 liters, and 1,630 liters, respectively. We measured the plasma concentrations of HCQ in patients with prophylactic failure of HCQ and compared them with the prediction intervals of the simulated concentrations for HCQ from the final PK model built in this study. In 71% of the patients with prophylactic failure, the plasma concentrations of HCQ were below the lower bounds of the 95% prediction interval, while only 8% of them showed higher levels than the upper bounds of the 95% prediction interval. We report that a significant cause of prophylactic failure among the individuals in ROKA was ascribed to plasma concentrations of HCQ lower than those predicted by the PK model. However, prophylactic failure despite sufficient plasma concentrations of HCQ was confirmed in several individuals, warranting continued surveillance to monitor changes in the HCQ susceptibility of Plasmodium vivax in the Republic of Korea.
ISSN
0066-4804
Language
English
URI
http://hdl.handle.net/10371/78135
DOI
https://doi.org/10.1128/AAC.00339-08
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College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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