Population pharmacokinetics of piperaquine in adults and children with uncomplicated falciparum or vivax malaria.

Abstract

AIMS:

To study the population pharmacokinetics of piperaquine after co-administration with dihydroartemisinin in uncomplicated malaria.

METHODS:

The disposition of piperaquine was studied in 85 Cambodian patients with uncomplicated falciparum or vivax malaria treated with the piperaquine-dihydroartemisinin coformulation Artekin. All patients were given Artekin orally at 0, 6, 24 and 32 h with a total piperaquine dose of 32-35 mg base kg-1. Adults were given tablets while children received either tablets or a dispersible granule formulation. Patients underwent either intensive (17-19 samples) or sparse (2-5 samples) blood sampling schedules over 35 days and clinical/parasitological follow-up over > 28 days. Piperaquine in plasma was quantified by high performance liquid chromatography.

RESULTS:

All patients achieved fever clearance within 24 h and parasite clearance within 72 h. The 28-day cure rate was 97% in adults and 98% in children. A covariate-free two-compartment population model with first-order absorption and elimination gave the most robust representation of the plasma concentration-time data in both adults and children. In adults (n = 38), the median (interquartile range) derived pharmacokinetic descriptors CL/F, Vss/F and t1/2,z were 0.9 l h-1 kg-1 (0.79-1.02 l h-1 kg-1), 574 l kg-1(371-711 l kg-1) and 23 days (19-28 days), respectively. In children (n = 47), corresponding values were 1.8 l h-1 kg-1 (1.29-2.3 l h-1 kg-1), 614 l kg-1 (332-1205 l kg-1) and 14 days (10-18 days), respectively.

CONCLUSIONS:

Piperaquine is a highly lipid-soluble drug with a large Vss/F, long t1/2,z and a clearance that is markedly higher in children than in adults.

• Authors: Te-Yu Hung, Timothy M E Davis, Kenneth F Ilett, Harin Karunajeewa, Sean Hewitt, Mey Bouth Denis, Chiv Lim, Doung Socheat
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 57 Issue 3 Pg. 253-62 (Mar 2004) ISSN: 0306-5251 [Print] England
• PMID: 14998421 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Quinolines
• Tablets
• piperaquine

Topics

• Adult
• Antimalarials (pharmacokinetics, therapeutic use)
• Child
• Dose-Response Relationship, Drug
• Female
• Humans
• Malaria, Falciparum (blood, drug therapy)
• Malaria, Vivax (blood, drug therapy)
• Male
• Quinolines (pharmacokinetics, therapeutic use)
• Tablets