Open-Label Crossover Study of Primaquine and Dihydroartemisinin-Piperaquine Pharmacokinetics in Healthy Adult Thai Subjects

被引:37
作者
Hanboonkunupakarn, Borimas [1 ]
Ashley, Elizabeth A. [2 ,3 ]
Jittamala, Podjanee [1 ]
Tarning, Joel [2 ,3 ]
Pukrittayakamee, Sasithon [1 ]
Hanpithakpong, Warunee [2 ]
Chotsiri, Palang [2 ]
Wattanakul, Thanaporn [2 ]
Panapipat, Salwaluk [2 ]
Lee, Sue J. [2 ,3 ]
Day, Nicholas P. J. [2 ,3 ]
White, Nicholas J. [2 ,3 ]
机构
[1] Mahidol Univ, Fac Trop Med, Bangkok, Thailand
[2] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand
[3] Univ Oxford, Ctr Trop Med, Nuffield Dept Med, Oxford, England
基金
英国惠康基金;
关键词
MASS-SPECTROMETRIC METHOD; PLASMODIUM-FALCIPARUM; SAFETY EVALUATION; BIOAVAILABILITY; ARTESUNATE; MALARIA; VIVAX; FAT;
D O I
10.1128/AAC.03704-14
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Dihydroartemisinin-piperaquine is an artemisinin-based combination treatment (ACT) recommended by the WHO for uncomplicated Plasmodium falciparum malaria, and it is being used increasingly for resistant vivax malaria where combination with primaquine is required for radical cure. The WHO recently reinforced its recommendations to add a single dose of primaquine to ACTs to reduce P. falciparum transmission in low-transmission settings. The pharmacokinetics of primaquine and dihydroartemisinin-piperaquine were evaluated in 16 healthy Thai adult volunteers in a randomized crossover study. Volunteers were randomized to two groups of three sequential hospital admissions to receive 30 mg (base) primaquine, 3 tablets of dihydroartemisinin-piperaquine (120/960 mg), and the drugs together at the same doses. Blood sampling was performed over 3 days following primaquine and 36 days following dihydroartemisinin-piperaquine dosing. Pharmacokinetic assessment was done with a noncompartmental approach. The drugs were well tolerated. There were no statistically significant differences in dihydroartemisinin and piperaquine pharmacokinetics with or without primaquine. Dihydroartemisinin-piperaquine coadministration significantly increased plasma primaquine levels; geometric mean ratios (90% confidence interval [CI]) of primaquine combined versus primaquine alone for maximum concentration (C-max), area under the concentration-time curve from 0 h to the end of the study (AUC(0-last)), and area under the concentration-time curve from 0 h to infinity (AUC(0-infinity)) were 148% (117 to 187%), 129% (103 to 163%), and 128% (102 to 161%), respectively. This interaction is similar to that described recently with chloroquine and may result in an enhanced radical curative effect.
引用
收藏
页码:7340 / 7346
页数:7
相关论文
共 32 条
  • [1] A Small Amount of Fat Does Not Affect Piperaquine Exposure in Patients with Malaria
    Annerberg, Anna
    Lwin, Khin Maung
    Lindegardh, Niklas
    Khrutsawadchai, Sakchai
    Ashley, Elizabeth
    Day, Nicholas P. J.
    Singhasivanon, Pratap
    Tarning, Joel
    White, Nicholas J.
    Nosten, Francois
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2011, 55 (09) : 3971 - 3976
  • [2] [Anonymous], 2012, UPD WHO POL REC OCT
  • [3] [Anonymous], 2010, Guidelines for the treatment of Malaria, DOI DOI 10.1080/03630269.2023.2168201
  • [4] Baird JK, 2003, CLIN INFECT DIS, V37, P1659, DOI 10.1086/379714
  • [5] STUDIES ON THE CHEMOTHERAPY OF THE HUMAN MALARIAS .7. THE ANTIMALARIAL ACTIVITY OF PAMAQUINE
    BERLINER, RW
    EARLE, DP
    TAGGART, JV
    WELCH, WJ
    ZUBROD, CG
    KNOWLTON, P
    ATCHLEY, JA
    SHANNON, JA
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1948, 27 (03) : 108 - 113
  • [6] CHEN G, 1947, J PHARMACOL EXP THER, V91, P133
  • [7] Pharmacokinetics and Ex Vivo Pharmacodynamic Antimalarial Activity of Dihydroartemisinin-Piperaquine in Patients with Uncomplicated Falciparum Malaria in Vietnam
    Dao Van Hoang Nguyen
    Quoc Phuc Nguyen
    Ngoa Dang Nguyen
    Thuy Thi Thanh Le
    The Duy Nguyen
    Duy Ngoc Dinh
    Thanh Xuan Nguyen
    Dai Bui
    Chavchich, Marina
    Edstein, Michael D.
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2009, 53 (08) : 3534 - 3537
  • [8] Artemisinin combination therapy for vivax malaria
    Douglas, Nicholas M.
    Anstey, Nicholas M.
    Angus, Brian J.
    Nosten, Francois
    Price, Ric N.
    [J]. LANCET INFECTIOUS DISEASES, 2010, 10 (06) : 405 - 416
  • [9] INTERACTIONS AMONG PRIMAQUINE, MALARIA INFECTION AND OTHER ANTIMALARIALS IN THAI SUBJECTS
    EDWARDS, G
    MCGRATH, CS
    WARD, SA
    SUPANARANOND, W
    YAKAMEE, SP
    DAVIS, TME
    WHITE, NJ
    [J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1993, 35 (02) : 193 - 198
  • [10] Short report: Lack of sex effect on the pharmacokinetics of primaquine
    Elmes, NJ
    Bennett, SM
    Abdalla, H
    Carthew, TL
    Edstein, MD
    [J]. AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 2006, 74 (06) : 951 - 952