Comparison of the ECG Effects Related to Pharmacokinetic Profile of Chloroquine and Piperaquine

Chloroquine and piperaquine are the two most widely used antimalarial drugs ever. Hundreds of millions of people have received these drugs. Both are structurally similar and have cardiovascular effect. While there are no concerns over the use of chloroquine, regulatory authorities have suggested restrictions on the use of piperaquine. We have recently completed a series of cross-over clinical and pharmacokinetic evaluations of chloroquine, piperaquine, pyronaridine and primaquine in healthy subjects. These studied were approved by the ethical committee of FTM. All drugs were well tolerated with no clinically significant ECG changes. Four subjects were in two studies. This offers a unique opportunity to compare the electrocardiographic effects of chloroquine and piperaquine in the same subjects and therefore characterize the concentration-effect relationships, and thus relative safety. We propose to extend the previous subject study to recruit 16 subjects including those who have received either piperaquine or chloroquine in our previous studies so that 20 subjects received both drugs for a crossover comparison. The blood sampling schedule and electrocardiograms would be exactly the same as previously but would finish at 24 hours.