Pharmacokinetics of propantheline bromide in normal man.

Six normal men were administered propantheline bromide (15 mg) in single doses intravenously, and as an oral solution in a balanced random crossover study. Plasma concentrations and urinary excretion of the drug were measured after each treatment, using a stable isotope dilution assay. Initial plasma concentrations of propantheline bromide ranged from 494 to 1310 ng ml 3 min after the intravenous dose. Plasma levels of the drug decreased rapidly to reach concentrations of 4.5 to 27.2 ng ml 4 h after dosage. A total of 17.3% (range 8.73 to 23.69%) of the intravenous propantheline bromide was eliminated by excretion in urine. Pharmacokinetic analysis of these data indicated mean biological half-lives of 3.2 min (range 1.2 to 4.2 min; distribution phase) 57.9 min (range 12.6 to 106.2 min; fast elimination phase) and 2.93 h (range 2.16 to 3.69 h; slow elimination phase). Total plasma clearance was calculated as 79.2 l h (range 28.1 to 137.7 l h) and the renal clearance was 11.5 l h (range 6.7 to 15.7 l h) demonstrating the importance of extra-renal routes in the elimination of propantheline bromide. Following the oral dose of propantheline bromide plasma concentrations of the drug were at or below the precision level of the assay (5 ng ml) at all times after dosage. A total of 1.08% (range 0.33 to 2.05%) of the propantheline bromide administered was excreted in urine. The results of this study show that propantheline bromide was rapidly distributed and eliminated in man, and that extra-renal routes (probably metabolism) were the major pathways of elimination. Comparison of the data obtained following oral and intravenous administration indicate a low systemic availability of orally administered propantheline bromide. This may reflect the importance of the extra-renal routes of elimination in a `first-pass' effect for the drug.