WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The absolute bioavailability of imidafenacin in rats and dogs is 5.6% and 36.1%, respectively. The pharmacokinetic profiles of imidafenacin after oral administration have been revealed. Imidafenacin is primarily metabolized to metabolites by CYP3A4 and UGT1A4. WHAT THIS STUDY ADDS: The absolute bioavailability of imidafenacin in human is 57.8%. The pharmacokinetic profiles of imidafenacin after intravenous administration are revealed. The formation of metabolites in the plasma is caused mainly by first-pass effects. AIMS: To investigate the absolute bioavailability of imidafenacin, a new muscarinic receptor antagonist, a single oral dose of 0.1 mg imidafenacin was compared with an intravenous (i.v.) infusion dose of 0.028 mg of the drug in healthy subjects. METHODS:Fourteen healthy male subjects, aged 21-45 years, received a single oral dose of 0.1 mg imidafenacin or an i.v. infusion dose of 0.028 mg imidafenacin over 15 min at two treatment sessions separated by a 1-week wash-out period. Plasma concentrations of imidafenacin and the major metabolites M-2 and imidafenacin-N-glucuronide (N-Glu) were determined. The urinary excretion of imidafenacin was also evaluated. Analytes in biological samples were measured by liquid chromatography tandem mass spectrometry. RESULTS: The absolute oral bioavailability of imidafenacin was 57.8% (95% confidence interval 54.1, 61.4) with a total clearance of 29.5 +/- 6.3 l h(-1). The steady-state volume of distribution was 122 +/- 28 l, suggesting that imidafenacin distributes to tissues. Renal clearance after i.v. infusion was 3.44 +/- 1.08 l h(-1), demonstrating that renal clearance plays only a minor role in the elimination of imidafenacin. The ratio of AUC(t) of both M-2 and N-Glu to that of imidafenacin was reduced after i.v. infusion from that seen after oral administration, suggesting that M-2 and N-Glu in plasma after oral administration were generated primarily due to first-pass metabolism. No serious adverse events were reported during the study. CONCLUSIONS: The absolute mean oral bioavailability of imidafenacin was determined to be 57.8%. Imidafenacin was well tolerated following both oral administration and i.v. infusion.
RCT Entities:
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The absolute bioavailability of imidafenacin in rats and dogs is 5.6% and 36.1%, respectively. The pharmacokinetic profiles of imidafenacin after oral administration have been revealed. Imidafenacin is primarily metabolized to metabolites by CYP3A4 and UGT1A4. WHAT THIS STUDY ADDS: The absolute bioavailability of imidafenacin in human is 57.8%. The pharmacokinetic profiles of imidafenacin after intravenous administration are revealed. The formation of metabolites in the plasma is caused mainly by first-pass effects. AIMS: To investigate the absolute bioavailability of imidafenacin, a new muscarinic receptor antagonist, a single oral dose of 0.1 mg imidafenacin was compared with an intravenous (i.v.) infusion dose of 0.028 mg of the drug in healthy subjects. METHODS: Fourteen healthy male subjects, aged 21-45 years, received a single oral dose of 0.1 mg imidafenacin or an i.v. infusion dose of 0.028 mg imidafenacin over 15 min at two treatment sessions separated by a 1-week wash-out period. Plasma concentrations of imidafenacin and the major metabolites M-2 and imidafenacin-N-glucuronide (N-Glu) were determined. The urinary excretion of imidafenacin was also evaluated. Analytes in biological samples were measured by liquid chromatography tandem mass spectrometry. RESULTS: The absolute oral bioavailability of imidafenacin was 57.8% (95% confidence interval 54.1, 61.4) with a total clearance of 29.5 +/- 6.3 l h(-1). The steady-state volume of distribution was 122 +/- 28 l, suggesting that imidafenacin distributes to tissues. Renal clearance after i.v. infusion was 3.44 +/- 1.08 l h(-1), demonstrating that renal clearance plays only a minor role in the elimination of imidafenacin. The ratio of AUC(t) of both M-2 and N-Glu to that of imidafenacin was reduced after i.v. infusion from that seen after oral administration, suggesting that M-2 and N-Glu in plasma after oral administration were generated primarily due to first-pass metabolism. No serious adverse events were reported during the study. CONCLUSIONS: The absolute mean oral bioavailability of imidafenacin was determined to be 57.8%. Imidafenacin was well tolerated following both oral administration and i.v. infusion.
Authors: Paul Abrams; Linda Cardozo; Magnus Fall; Derek Griffiths; Peter Rosier; Ulf Ulmsten; Philip Van Kerrebroeck; Arne Victor; Alan Wein Journal: Urology Date: 2003-01 Impact factor: 2.649
Authors: W F Stewart; J B Van Rooyen; G W Cundiff; P Abrams; A R Herzog; R Corey; T L Hunt; A J Wein Journal: World J Urol Date: 2002-11-15 Impact factor: 4.226
Authors: Teh-Wei Hu; Todd H Wagner; Judith D Bentkover; Kristi LeBlanc; Amy Piancentini; Walter F Stewart; Ron Corey; Steve Z Zhou; Timothy L Hunt Journal: Urology Date: 2003-06 Impact factor: 2.649