title: Pharmacokinetic Interactions Between Quinine and Lopinavir/Ritonavir in Healthy Thai Adults.
abstract: This study aimed to investigate the pharmacokinetic interactions between quinine and lopinavir boosted with ritonavir (LPV/r) in healthy Thai adults (8 males and 12 females). Period 1 (day 1): subjects received a single oral dose of 600 mg quinine sulfate. Period 2: subjects received LPV/r (400/100 mg) twice daily. Period 3: subjects received a single quinine sulfate dose plus LPV/r twice a day. Intensive blood sampling was performed during each phase. Quinine AUC0-48h (area under the plasma concentration-time curve from time 0 to 48 hours), AUC0-∞ (area under the plasma concentration-time curve from time 0 to infinity), and Cmax (maximum concentration over the time-span specified), were 56%, 57%, and 47% lower, respectively, in the presence of LPV/r. 3-Hydroxyquinine AUC0-48h, AUC0-∞, and Cmax were significantly lower and the metabolite-to-parent ratio was significantly reduced. Lopinavir and ritonavir exposures were not significantly reduced with quinine coadministration, but Cmax of both drugs were significantly lower. The geometric mean ratio (GMR) and 90% CI of AUC0-48h, AUC0-∞, and Cmax for quinine, 3-hydroxyquinine, lopinavir, and ritonavir lay outside the bioequivalent range of 0.8-1.25. Drug treatments during all periods were generally well tolerated. The reduction in systemic exposure of quinine and 3-hydroxyquinine with concomitant LPV/r use raises concerns of suboptimal exposure. Studies in HIV/malaria coinfection patients are needed to determine the clinical impact to decide if any change to the quinine dose is warranted.
authors.affiliation: Faculty of Science and Technology, Chiang Mai Rajabhat University, Chaing Mai, Thailand; Program for HIV Prevention and Treatment, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Harvard School of Public Health, Boston, Massachusetts; Mae Sot General Hospital, Tak Province, Thailand; Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University, Pathumthani, Thailand; Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand.
authors.forename: Siwalee
authors.initials: S
authors.lastname: Rattanapunya
authors.affiliation: Faculty of Science and Technology, Chiang Mai Rajabhat University, Chaing Mai, Thailand; Program for HIV Prevention and Treatment, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Harvard School of Public Health, Boston, Massachusetts; Mae Sot General Hospital, Tak Province, Thailand; Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University, Pathumthani, Thailand; Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand.
authors.forename: Tim R
authors.initials: TR
authors.lastname: Cressey
authors.affiliation: Faculty of Science and Technology, Chiang Mai Rajabhat University, Chaing Mai, Thailand; Program for HIV Prevention and Treatment, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Harvard School of Public Health, Boston, Massachusetts; Mae Sot General Hospital, Tak Province, Thailand; Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University, Pathumthani, Thailand; Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand.
authors.forename: Ronnatrai
authors.initials: R
authors.lastname: Rueangweerayut
authors.affiliation: Faculty of Science and Technology, Chiang Mai Rajabhat University, Chaing Mai, Thailand; Program for HIV Prevention and Treatment, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Harvard School of Public Health, Boston, Massachusetts; Mae Sot General Hospital, Tak Province, Thailand; Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University, Pathumthani, Thailand; Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand.
authors.forename: Yardpiroon
authors.initials: Y
authors.lastname: Tawon
authors.affiliation: Faculty of Science and Technology, Chiang Mai Rajabhat University, Chaing Mai, Thailand; Program for HIV Prevention and Treatment, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Harvard School of Public Health, Boston, Massachusetts; Mae Sot General Hospital, Tak Province, Thailand; Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University, Pathumthani, Thailand; Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand.
authors.forename: Panida
authors.initials: P
authors.lastname: Kongjam
authors.affiliation: Faculty of Science and Technology, Chiang Mai Rajabhat University, Chaing Mai, Thailand; Program for HIV Prevention and Treatment, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Harvard School of Public Health, Boston, Massachusetts; Mae Sot General Hospital, Tak Province, Thailand; Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University, Pathumthani, Thailand; Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand kesaratmu@yahoo.com.
authors.forename: Kesara
authors.initials: K
authors.lastname: Na-Bangchang
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D061466:Lopinavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011803:Quinine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000962:Antimalarials; D017320:HIV Protease Inhibitors; D061466:Lopinavir; D011803:Quinine; D019438:Ritonavir