In:
British Journal of Clinical Pharmacology, Wiley, Vol. 76, No. 6 ( 2013-12), p. 858-867
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0306-5251
,
1365-2125
DOI:
10.1111/bcp.2013.76.issue-6
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
1498142-7
SSG:
15,3
Permalink