Pharmacokinetics and safety of nifedipine GITS/candesartan fixed-dose combination in subjects with hepatic impairment

First published in Int. Journal of Clinical Pharmacology and Therapeutics on 2017 Mar
Int J Clin Pharmacol Ther. 2017 Mar;55(3):246-255. doi: 10.5414/CP202700.

Authors: Liu Y, Boettcher MF, Schmidt A, Unger S, Halabi A, Brendel E, Blode H

Abstract

Objective:

To investigate the pharmacokinetic (pharmacokinetics) profiles and safety of nifedipine and candesartan after a single oral dose of nifedipine gastrointestinal therapeutic system (GITS) 30 mg/candesartan cilexetil 8 mg (N30/C8 mg) fixed-dose combination (FDC) in adults with mild to moderate hepatic impairment.

Methods:

A phase I, single-center, non-randomized, non-controlled, non-blinded, observational study (N = 32). pharmacokinetics profiles for nifedipine and candesartan were assessed in patients with mild (Child-Pugh A; group 1) or moderate (Child-Pugh B; group 2) hepatic impairment and compared with age- and gender-matched healthy controls (groups 3 and 4) following a single dose of N30/C8 FDC. Safety and tolerability were assessed throughout the study.

Results:

On average, area under the plasma concentration vs. time curves (AUC) for nifedipine increased 93% and 253% in mild and moderate hepatic impairment, while maximum plasma concentrations (Cmax) increased 64% and 171%, respectively. AUC values for candesartan increased 19% and 92%, while Cmax values increased 3% and 11%, respectively. In subjects with or without liver impairment, adverse event rates were similar and consistent with the known side-effect profiles of nifedipine GITS and candesartan as monotherapies.

Conclusion:

Careful monitoring, and, if necessary, dose adjustment according to response and tolerability may be required for nifedipine GITS/candesartan FDC in patients with mild and moderate hepatic impairment.

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