A Comprehensive Review on the Pharmacokinetics and Bioanalysis of Piperaquine

Piperaquine is an important partner drug in artemisinin-based combination therapy, which is highly effective for the treatment of uncomplicated malaria. Several studies have been reported on its pharmacokinetic profiles in different populations, as well as its bioanalytical methods. Piperaquine shows a very large volume of distribution (up to 877 l/kg), a low oral clearance (0.3-1.9 l/h/kg), and an extremely long terminal elimination half-life (up to 30 days) in both healthy volunteers and malarial patients. Piperaquine metabolism is primarily mediated by CYP3A4, and to a lesser extent by CYP2D6 and CYP2C8. The oral bioavailability of piperaquine can be influenced by the consumption of high-fat food. The pharmacokinetics of piperaquine is affected by body weight, age, and pregnancy. Piperaquine has limited clinically relevant interactions with most commonly prescribed drugs. Plasma has been the most commonly studied matrix, and the most used pretreatment techniques involve protein precipitation. HPLC-UV and HPLC-MS/MS are usually used for the quantification of piperaquine in biological samples with researchers seeking a balance between affordability and sensitivity. This review summarizes the analytical assays used for the quantification of piperaquine in biological samples and its pharmacokinetic properties, with particular attention to information on food–drug interactions, drug-drug interactions, and pharmacokinetic characteristics in special populations, including pregnant women and children.