title: The influence of food on the pharmacokinetics of piperaquine in healthy Vietnamese volunteers.
abstract: The combination piperaquine and dihydroartemisinin is emerging as first line treatment of uncomplicated falciparum malaria in Southeast Asia. The aim of this study was to determine the influence of a standard Vietnamese meal on the single-dose pharmacokinetics of piperaquine when administered in combination with dihydroartemisinin, and to gain extended data on the terminal half-life of piperaquine in healthy Vietnamese volunteers. Subjects were randomly assigned to take a single oral dose of piperaquine phosphate (640 mg)+dihydroartemisinin (80 mg) together with a standardized Vietnamese meal (n=16) or to remain fasting for 4h following drug intake (n=16). Frequent blood sampling was conducted during 36 h, followed by weekly samples for 7 weeks. The pharmacokinetic parameters of piperaquine were determined by noncompartmental analysis. The median (80% central range) AUC(0-last) was 11.5 (6.9-17.3)h mg/L in fed and 13.9 (2.8-19.3)h mg/L in fasting subjects, indicating a considerable variability in exposure in both groups. The estimated overall oral clearance was 0.27 (0.12-1.49)L/(h kg), the volume of distribution during the terminal elimination phase was 230 (102-419)L/kg and estimated terminal half-life was 18 (5-93) days. This study did not demonstrate a significant impact of a standardized Vietnamese meal on the oral absorption of piperaquine.
authors.affiliation: Pharmaceutical Unit, Department of Malaria Treatment and Research, National Institute of Malariology, Parasitology and Entomology, Tu liem, Hanoi, Viet Nam.
authors.forename: Trinh Ngoc
authors.initials: TN
authors.lastname: Hai
authors.forename: Sofia Friberg
authors.initials: SF
authors.lastname: Hietala
authors.forename: Nguyen
authors.initials: N
authors.lastname: Van Huong
authors.forename: Michael
authors.initials: M
authors.lastname: Ashton
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D037621:Artemisinins / Q000008:administration & dosage; D001682:Biological Availability; D004359:Drug Therapy, Combination; D005215:Fasting; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008460:Meat; D008875:Middle Aged; D010063:Ovum; D011804:Quinolines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014675:Vegetables; D014744:Vietnam; D014838:Volunteers; D010879:Piperazines
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines