Pharmacokinetics and pharmacodynamics of R- and S-gallopamil during multiple dosing

Aims Using a stable isotope technique we investigated the pharmacokinetics and pharmacodynamics of gallopamil after administration of 50 mg pseudorace mic gallopamil every 12 h for 7 doses (72 h). Methods Six male healthy volunteers were studied, After the seventh dose th e pharmacokinetics and pharmacodynamics were assessed. Serum levels of gall opamil were measured by gas chromatography/mass spectrometry. Effects of ga llopamil were measured by ECG recording. Results The apparent oral clearances (R: 4.8 l min(-1) (95% CI: 2.9-6.8); S : 5.5 1 min(-1) (95% CI: 2.5-8.5)) and half-lives (R: 6.2 h; S: 7.2 h) of R - and S-gallopamil were similar (P>0.05). The serum protein binding (f(u) R : 0.035 (95% CI: 0.026-0.045); S: 0.051 (95% CI: 0.033-0.069)) and the rena l elimination (% of dose R: 0.49%; S: 0.71%) were enantioselective. Gallopa mil had a potent effect on the PR interval (% prolongation 35.7% (95% CI: 1 4.0-57.3)). No changes in other electrocardiographic or cardiovascular para meters were observed. Conclusions The pharmacokinetics and bioavailability of the racemic drug ga llopamil are not stereoselective at steady-state and are therefore not subs tantially altered compared with the single dose administration of gallopami l.