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 concentration-time data were used to generate a data set including 42 subjects (34 males, 8 females) with varying degrees of renal function (average of two estimated creatinine clearance rates of 10 to 112 mL/min). Age ranged from 19 to 88 years. Subjects received single oral doses (range: 2.5-20 mg) of pilocarpine. 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 administration. 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 determined by gas chromatography/ mass spectrometry. The pharmacokinetic parameters (elimination rate constant, C max , t max , AUC, Vd/F, and Cl/F) in subjects with impaired renal function were similar to results found in other pharmacokinetic studies involving normal healthy volunteers with only C max being significantly higher (p < 0.05). No significant regression relationships were noted between creatinine clearance and pilocarpine elimination rate constant, t max , Vd/F, Cl/F, or AUC. Pilocarpine clearance does not appear to be impaired in patients with varying degrees of renal insufficiency.