This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lim, H.-S.
Right arrow Articles by Park, J.-W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lim, H.-S.
Right arrow Articles by Park, J.-W.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, April 2009, p. 1468-1475, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.00339-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

Hyeong-Seok Lim,1,{dagger} Jeong-Soo Im,2,{dagger} Joo-Youn Cho,3 Kyun-Seop Bae,1 Terry A. Klein,4 Joon-Sup Yeom,5 Tae-Seon Kim,6 Jae-Seon Choi,6 In-Jin Jang,3 and Jae-Won Park6*

Department of Pharmacology, Ulsan University College of Medicine, 388-1 Pungnap-2-dong, Songpa-gu, Seoul 138-736, Republic of Korea,1 Department of Preventive Medicine,2 Department of Microbiology, Graduate School of Medicine, Gachon University of Medicine and Science, 1198 Kuwol-1-dong, Namdong-gu, Incheon 405-760, Republic of Korea,6 Department of Pharmacology, Seoul National University College of Medicine, 28 Yeongeon-dong, Jongno-gu, Seoul 110-799, Republic of Korea,3 Force Health Protection, 18th Medical Command, Unit 15281, APO AP 96205-5281, Yongsan-gu, Seoul, Republic of Korea,4 Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 108 Pyung-dong, Jongro-gu, Seoul 110-748, Republic of Korea5

Received 11 March 2008/ Returned for modification 2 July 2008/ Accepted 17 January 2009

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.

* Corresponding author. Mailing address: Department of Microbiology, Graduate School of Medicine, Gachon University of Medicine and Science, 1198, Kuwol-1-dong, Namdong-gu, Incheon 405-760, Republic of Korea. Phone: (82)-32-460-2184. Fax: (82)-32-421-5537. E-mail: seorak{at}dreamwiz.com

{triangledown} Published ahead of print on 2 February 2009.

{dagger} Hyeong-Seok Lim and Jeong-Soo Im contributed equally to this work.

Antimicrobial Agents and Chemotherapy, April 2009, p. 1468-1475, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.00339-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jun, G., Yeom, J.-S., Hong, J.-Y., Shin, E-H., Chang, K.-S., Yu, J.-R., Oh, S., Chung, H., Park, J.-W. (2009). Resurgence of Plasmodium vivax Malaria in the Republic of Korea during 2006-2007. Am J Trop Med Hyg 81: 605-610 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»