Oral pharmacokinetics of pirenzepine in man following single and multiple doses

The relative bioavailability of pirenzepine tablets (50 mg and two 25 mg) was assessed in 18 subjects in a single dose crossover study. The relative bioavailability of the tablet formulations, compared to a 50 mg oral reference solution given in the fasted state, was unity. The parameters of area under the curve, peak pirenzepine plasma concentration and time-to-peak demonstrated no significant difference for tablet formulations as compared to a 50 mg oral reference solution. After single oral dosing, the harmonic mean half-life of pirenzepine was 10.2 h. The mean renal clearance of 110 ± 12 ml/min approximated glomerular filtration rate. Twelve of the 18 subjects were administered the 50 mg tablet every 8 h for 6 days to assess the multiple dose pharmacokinetics of oral pirenzepine. Drug accumulation to steady state occurred within 4 half-lives as predicted from single dose data. The harmonic mean half-life of pirenzepine after multiple oral dosing was 12.4 h.