Pitfalls in estimating piperaquine elimination

Abstract

By using a sensitive new assay, the terminal elimination half-life of the antimalarial piperaquine in a healthy volunteer was estimated to be 33 days, which is longer than estimated previously. This result illustrates the importance of extended sampling duration and sensitive assay methodologies in characterizing the disposition of slowly eliminated antimalarial drugs.

FIG. 1.

PQ concentration-time profile for plasma and blood from a healthy Caucasian male volunteer after a single oral dose of DHA-PQ (three tablets, each containing 320 mg of PQ phosphate and 40 mg of DHA) together with a fatty meal.

FIG. 2.

Antimalarial pharmacodynamics. Elimination of piperaquine, illustrating the different estimates of the terminal elimination half-life as a function of follow-up duration and assay sensitivity. The inset illustrates potential problems with an insufficient follow-up period for drugs with multiphasic elimination kinetics and a long terminal half-life.