Effects of ketoconazole treatment on the pharmacokinetics of safinamide and its plasma metabolites in healthy adult subjects.

Abstract:

:The purpose of this mechanistic drug interaction study was to investigate the effects of ketoconazole on the pharmacokinetics of safinamide. Ketoconazole was applied as a potent prototypic inhibitor of cytochrome CYP3A4, to determine the role of CYP3A4 in the metabolic clearance of safinamide. In an open-label, randomized, two-period, two-sequence cross-over study, 14 healthy adult subjects (7 males/7 females) received two single doses of 100 mg safinamide: alone and on top of multiple doses of ketoconazole (200 mg b.i.d.) given over 6 days. Serial blood samples were collected over 240 h post dose to quantify safinamide parent drug and metabolite concentrations for pharmacokinetic evaluation. Safinamide exposure was essentially unchanged when administered with and without ketoconazole: C(max) and AUC(0-∞) point estimates (90% CIs) for the treatment comparison were 106.6 (101.0; 112.4) and 112.9 (109.8; 116.03), respectively. Similarly, ketoconazole did not influence the formation and clearance of safinamide metabolites to a clinically relevant extent. Overall, the study shows that CYP3A4 plays a minor role in the metabolism of safinamide in vivo. Therefore, safinamide can be administered together with potent CYP3A4 inhibitors without any requirement for dose adjustment.

journal_name

Biopharm Drug Dispos

authors

Krösser S,Marquet A,Gallemann D,Wolna P,Fauchoux N,Hermann R,Johne A

doi

10.1002/bdd.1822

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

550-9

issue

9

eissn

0142-2782

issn

1099-081X

journal_volume

33

pub_type

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