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

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Published inAntimicrobial Agents and Chemotherapy Vol. 53; no. 4; pp. 1468 - 1475
Main Authors Lim, Hyeong-Seok, Im, Jeong-Soo, Cho, Joo-Youn, Bae, Kyun-Seop, Klein, Terry A., Yeom, Joon-Sup, Kim, Tae-Seon, Choi, Jae-Seon, Jang, In-Jin, Park, Jae-Won
Format Journal Article
LanguageEnglish
Published Washington, DC American Society for Microbiology 01.04.2009
American Society for Microbiology (ASM)
Subjects
Adult
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimalarials
Antimalarials - pharmacokinetics
Area Under Curve
Biological and medical sciences
Female
Human protozoal diseases
Humans
Hydroxychloroquine
Hydroxychloroquine - pharmacokinetics
Hydroxychloroquine - therapeutic use
Infectious diseases
Malaria
Malaria - prevention & control
Male
Medical sciences
Middle Aged
Models, Biological
Parasitic diseases
Pharmacology
Pharmacology. Drug treatments
Plasmodium vivax
Plasmodium vivax - drug effects
Protozoal diseases
Korea, Rep
Protozoa
Antimalarial
Apicomplexa
Protozoal disease
Chemoprophylaxis
Malaria
Parasitosis
Infection
Prevention
Plasmodium vivax
Chemotherapy
Treatment
Hydroxychloroquine
Parasiticide
Antirheumatic agent
Pharmacokinetics
Online AccessGet full text

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Abstract Classifications Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue AAC About AAC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy AAC RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0066-4804 Online ISSN: 1098-6596 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to AAC .asm.org, visit: AAC       
AbstractList 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.
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.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.
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.
Classifications Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue AAC About AAC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy AAC RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0066-4804 Online ISSN: 1098-6596 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to AAC .asm.org, visit: AAC       
Author In-Jin Jang
Tae-Seon Kim
Terry A. Klein
Jeong-Soo Im
Hyeong-Seok Lim
Jae-Won Park
Joon-Sup Yeom
Jae-Seon Choi
Joo-Youn Cho
Kyun-Seop Bae
AuthorAffiliation 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 Korea 5
AuthorAffiliation_xml – name: 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 Korea 5
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  givenname: Tae-Seon
  surname: Kim
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1098-6596
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Issue 4
Keywords Protozoa
Antimalarial
Apicomplexa
Protozoal disease
Chemoprophylaxis
Malaria
Parasitosis
Infection
Prevention
Plasmodium vivax
Chemotherapy
Treatment
Hydroxychloroquine
Parasiticide
Antirheumatic agent
Pharmacokinetics
Language English
License CC BY 4.0
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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@dreamwiz.com
Hyeong-Seok Lim and Jeong-Soo Im contributed equally to this work.
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PublicationTitle Antimicrobial Agents and Chemotherapy
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Snippet Classifications Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit...
Hydroxychloroquine (HCQ) is an antimalarial drug used as chemoprophylaxis against malaria caused by Plasmodium vivax in the Republic of Korea Army (ROKA). In...
Hydroxychloroquine (HCQ) is an antimalarial drug used as chemoprophylaxis against malaria caused by Plasmodium vivax in the Republic of Korea Army (ROKA). In...
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StartPage 1468
SubjectTerms Adult
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimalarials
Antimalarials - pharmacokinetics
Area Under Curve
Biological and medical sciences
Female
Human protozoal diseases
Humans
Hydroxychloroquine
Hydroxychloroquine - pharmacokinetics
Hydroxychloroquine - therapeutic use
Infectious diseases
Malaria
Malaria - prevention & control
Male
Medical sciences
Middle Aged
Models, Biological
Parasitic diseases
Pharmacology
Pharmacology. Drug treatments
Plasmodium vivax
Plasmodium vivax - drug effects
Protozoal diseases
Title Pharmacokinetics of Hydroxychloroquine and Its Clinical Implications in Chemoprophylaxis against Malaria Caused by Plasmodium vivax
URI http://aac.asm.org/content/53/4/1468.abstract
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