Pharmacokinetics of propantheline bromide in normal man

1 Six normal men were administered propantheline bromide (15 mg) in single doses intravenously, and as an oral solution in a balanced random crossover study.

2 Plasma concentrations and urinary excretion of the drug were measured after each treatment, using a stable isotope dilution assay.

3 Initial plasma concentrations of propantheline bromide ranged from 494 to 1310 ng ml^-1 3 min after the intravenous dose. Plasma levels of the drug decreased rapidly to reach concentrations of 4.5 to 27.2 ng ml^-1 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.

4 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).

5 Total plasma clearance was calculated as 79.2 l h^-1 (range 28.1 to 137.7 l h^-1) and the renal clearance was 11.5 l h^-1 (range 6.7 to 15.7 l h^-1) demonstrating the importance of extra-renal routes in the elimination of propantheline bromide.

6 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^-1) 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.

7 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.