Pharmacokinetic Interactions and Safety Evaluations of Coadministered Tafenoquine and Chloroquine in Healthy Subjects

20 Nov 2013

Ann K Miller, Emma Harrell, Li Ye, Sharon Baptiste-Brown, Jörg-Peter Kleim, Colin Ohrt, Stephan Duparc, Jörg J Möhrle, Alison Webster, Sandra Stinnett, Arlene Hughes, Sandy Griffith, Andrew P Beelen

British Journal of Clinical Pharmacology

DOI: 10.1111/bcp.12160

Abstract

AIMS:

The long-acting 8-aminoquinoline tafenoquine (TQ) coadministered with chloroquine (CQ) may radically cure Plasmodium vivax malaria. Coadministration therapy was evaluated for a pharmacokinetic interaction, and pharmacodynamic, safety and tolerability characteristics.

METHODS:

Healthy subjects, 18-55 years old, without documented glucose-6-phosphate dehydrogenase deficiency received CQ alone (Days 1-2: 600 mg, Day 3: 300 mg), TQ alone (Days 2-3: 450 mg), or coadministration therapy (Day 1: CQ 600 mg; Day 2: CQ 600 mg+TQ 450 mg; Day 3: CQ 300 mg+TQ 450 mg) in a randomized, double-blind, parallel-group study. Blood samples for pharmacokinetic and pharmacodynamic analyses and safety data, including electrocardiograms, were collected for 56 days.

RESULTS:

CQ+TQ had no effect on TQ AUC0-t , AUC0-∞ , Tmax , or t1/2 . The 90% confidence intervals of CQ+TQ:TQ for AUC0-t , AUC0-∞ , and t1/2 indicated no drug interaction. On Day 2 of CQ+TQ coadministration, TQ Cmax and AUC0-24 increased 38% (90% CI 1.27,1.64) and 24% (90% CI 1.04,1.46), respectively. The pharmacokinetics of CQ and its primary metabolite desethylchloroquine were not affected by TQ. Coadministration had no clinically significant effect on QT intervals, and was well tolerated.

CONCLUSION:

No clinically significant safety or pharmacokinetic / pharmacodynamic interactions were observed with coadministered CQ and TQ in healthy subjects.

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