title: Oral pharmacokinetics of pirenzepine in patients with chronic renal insufficiency, failure, and maintenance haemodialysis.
abstract: The pharmacokinetic properties of pirenzepine following administration of a single, 50 mg oral dose were evaluated in three groups of subjects: group I, end stage renal disease requiring maintenance haemodialysis (CLCR 0 to 10 ml.min-1); group II, moderate renal insufficiency (CLCR 10 to 30 ml.min-1); and group III, mild renal dysfunction (CLCR 30 to 70 ml.min-1). Additionally, subjects in group I received a 50 mg dose on a non-dialysis day and at least one week later, a 50 mg dose during haemodialysis. There was a linear relationship (r = 0.97) between pirenzepine renal clearance and renal function as measured by creatinine clearance. The harmonic mean terminal half-life for pirenzepine was 17.3 h in subjects with end stage renal disease, 18.0 h in subjects with moderate renal insufficiency and 14.7 h in subjects with mild renal dysfunction. Haemodialysis reduced the level of circulating pirenzepine by approximately 25%. The mean arterial to venous plasma pirenzepine ratio during hemodialysis was 1.29 (range 1.02-1.56). Based on subjective reporting of adverse experiences and clinical observation, pirenzepine appeared to have had a wide margin of safety in these patients. Dry mouth was the most frequently reported adverse experience attributable to pirenzepine administration. A reduction in dose or dosing frequency may be warranted only in end state renal disease (CLCR 0 to 10 ml.min-1).
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, inc., Ridgefield, Connecticut.
authors.forename: T
authors.initials: T
authors.lastname: MacGregor
authors.forename: K
authors.initials: K
authors.lastname: Matzek
authors.forename: J
authors.initials: J
authors.lastname: Keirns
authors.forename: M
authors.initials: M
authors.lastname: Vinocur
authors.forename: A
authors.initials: A
authors.lastname: Chonko
mesh_terms: D000284:Administration, Oral; D000328:Adult; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy / Q000652:urine*; D008297:Male; D008875:Middle Aged; D010890:Pirenzepine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000652:urine; D006435:Renal Dialysis
chemical_list: D010890:Pirenzepine