title: Safety, tolerability, and single- and multiple-dose pharmacokinetics of piperaquine phosphate in healthy subjects.
abstract: Piperaquine phosphate is an orally active bisquinolone antimalarial drug that has been used for the past 3 decades. The authors report the safety, tolerability, and pharmacokinetics of piperaquine from a classical controlled phase I study. It was a double-blind, randomized, parallel-group, placebo-controlled, and single- and multiple-dose study. During the rising single-dose study, single ascending oral doses of 500, 750, 1000, 1250, and 1500 mg of piperaquine phosphate were administered, whereas in rising multiple-dose study, once-daily ascending oral doses of 500, 750, 1000, and 1500 mg were administered for 3 consecutive days. Pharmacokinetic analysis for both the rising single- and multiple-dose studies was done using the noncompartmental approach. The mean apparent terminal half-life ranged from 11 to 23 days. Increase in exposure was less than dose proportional and linear. Piperaquine concentrations were measurable up to 60 days postdose. Multiple peaks were observed in the plasma piperaquine concentration-time profiles and exhibited 3- to 7-fold accumulation following multiple dosing. Piperaquine was well tolerated following single and multiple doses.
authors.affiliation: Metabolism and Pharmacokinetics Department, Ranbaxy Research Laboratories, Gurgaon-122015, Haryana, India.
authors.forename: Tausif
authors.initials: T
authors.lastname: Ahmed
authors.forename: Pradeep
authors.initials: P
authors.lastname: Sharma
authors.forename: Anirudh
authors.initials: A
authors.lastname: Gautam
authors.forename: Brijesh
authors.initials: B
authors.lastname: Varshney
authors.forename: Monica
authors.initials: M
authors.lastname: Kothari
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Ganguly
authors.forename: Joerg J
authors.initials: JJ
authors.lastname: Moehrle
authors.forename: Jyoti
authors.initials: J
authors.lastname: Paliwal
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Saha
authors.forename: Vijay
authors.initials: V
authors.lastname: Batra
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006207:Half-Life; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011804:Quinolines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced; D010879:Piperazines
chemical_list: D000962:Antimalarials; D011804:Quinolines; D013607:Tablets; C034759:piperaquine; D010879:Piperazines