Premium
Pharmacokinetics and pharmacodynamics of R‐ and S‐gallopamil during multiple dosing
Author(s) -
Gross Annette S.,
Eichelbaum Michel,
Mörike Klaus,
Mikus Gerd
Publication year - 2000
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2000.00115.x
Subject(s) - gallopamil , pharmacokinetics , pharmacodynamics , pharmacology , dosing , bioavailability , chemistry , medicine , calcium , nifedipine
Aims Using a stable isotope technique we investigated the pharmacokinetics and pharmacodynamics of gallopamil after administration of 50 mg pseudoracemic gallopamil every 12 h for 7 doses (72 h). Methods Six male healthy volunteers were studied. After the seventh dose the pharmacokinetics and pharmacodynamics were assessed. Serum levels of gallopamil were measured by gas chromatography/mass spectrometry. Effects of gallopamil 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 l 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 renal elimination (% of dose R: 0.49%; S: 0.71%) were enantioselective. Gallopamil had a potent effect on the PR interval (% prolongation 35.7% (95% CI: 14.0–57.3)). No changes in other electrocardiographic or cardiovascular parameters were observed. Conclusions The pharmacokinetics and bioavailability of the racemic drug gallopamil are not stereoselective at steady‐state and are therefore not substantially altered compared with the single dose administration of gallopamil.