Pharmacokinetics of pilocarpine in subjects with varying degrees of renal function

Data from three separate single-center studies were combined to assess the pharmacokinetics of orally administered pilocarpine. Pilocarpine concentrat ion-time data were used to generate a data set including 42 subjects (34 ma les, 8 females) with varying degrees of renal function (average of two esti mated creatinine clearance rates of 10 to 112 mL/min). Age ranged from 19 t o 88 years. Subjects received single oral doses (range: 2.5-20 mg) of piloc arpine. Plasma samples were collected at time 0; at 20 and 40 minutes; and at 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours following dose administratio n. C-max and A UC were normalized to a 5 mg exposure in those subjects who received doses other than 5 mg. Plasma pilocarpine concentrations were dete rmined by gas chromatography/mass spectrometry. The pharmacokinetic paramet ers (elimination rate constant, C-max, t(max), AUG, Vd/F, and Cl/F) in subj ects with impaired renal function were similar to results found in other ph armacokinetic studies involving normal healthy volunteers with only C-max b eing significantly higher (p < 0. 05). No significant regression relationsh ips rr ere noted between creatinine clearance and pilocarpine elimination r ate constant, t(max), Vd/F, Cl/F, orAUC. Pilocarpine clearance does not app ear to be impaired in patients with varying degrees of renal insufficiency. (C)2000 the American College of Clinical Pharmacology.