Pharmacokinetics and pharmacodynamics of R- and S-gallopamil during multiple dosing.
OBJECTIVE
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 (fu 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.
Gross
A S
AS
Dr Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Auerbachstrasse 112, 70376 Stuttgart, Germany.
Eichelbaum
M
M
Mörike
K
K
Mikus
G
G
D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005711:Gallopamil / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D006261:Headache / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D013237:Stereoisomerism; D013997:Time Factors; D014316:Tritium
D002121:Calcium Channel Blockers; D014316:Tritium; D005711:Gallopamil