Pharmacokinetics and safety of propiverine in patients with fatty liver disease

Objective: The present study was designed to assess the pharmacokinetics of propiverine after single and multiple dosing in patients with and without fatty liver disease. Methods: The serum concentration-time curves of propiverine and its main me tabolite propiverine-N-oxide were investigated in 12 patients with mild to moderate impairment of liver function (mean antipyrine clearance 26.0 ml mi n-l) and in 12 controls (antipyrine clearance 42.8 ml.min(-1)). Subjects we re treated orally with propiverine hydrochloride (Mictonorm) for 5 days (15 mg t. i. d.) to reach steady state. Results: No significant differences were observed for propiverine and its m ain metabolite with regard to peak Serum concentration (C-max), area under the serum concentration-time curve (AUC) and elimination half-life (t(1/2)) Adverse events were reported by 12 patients. Five patients with fatty live r disease and seven patients with normal liver function complained of dry m outh and/or blurred vision. Al adverse events reported were transient and m ild. Conclusion: No pharmacokinetic differences relevant for safety were observe d, comparing patients with and without fatty liver disease following repeat ed oral administration of propiverine. Thus there seems to be no need to ad just the dose in patients with mild to moderate impairment of liver functio n.