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Pharmacokinetic interactions and safety evaluations of coadministered tafenoquine and chloroquine in healthy subjects
Author(s) -
Miller Ann K.,
Harrell Emma,
Ye Li,
BaptisteBrown Sharon,
Kleim JőrgPeter,
Ohrt Colin,
Duparc Stephan,
Möhrle Jörg J.,
Webster Alison,
Stinnett Sandra,
Hughes Arlene,
Griffith Sandy,
Beelen Andrew P.
Publication year - 2013
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12160
Subject(s) - pharmacokinetics , pharmacology , medicine , pharmacodynamics , tolerability , confidence interval , drug interaction , adverse effect
Aims The long‐acting 8‐aminoquinoline tafenoquine ( TQ ) coadministered with chloroquine ( CQ ) may radically cure P lasmodium vivax malaria. Coadministration therapy was evaluated for a pharmacokinetic interaction and for 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; and day 3, 300 mg), TQ alone (days 2 and 3, 450 mg) or coadministration therapy (day 1, CQ 600 mg; day 2, CQ 600 mg + TQ 450 mg; and 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 The coadministration of CQ + TQ had no effect on TQ AUC 0– t , AUC 0–∞ , T max or t 1/2 . The 90% confidence intervals of CQ + TQ vs . TQ for AUC 0– t , AUC 0–∞ and t 1/2 indicated no drug interaction. On day 2 of CQ + TQ coadministration, TQ C max and AUC 0–24 increased by 38% (90% confidence interval 1.27, 1.64) and 24% (90% confidence interval 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. Conclusions No clinically significant safety or pharmacokinetic/pharmacodynamic interactions were observed with coadministered CQ and TQ in healthy subjects.