PHARMACOKINETICS OF THE ENANTIOMERS OF VERAPAMIL AFTER INTRAVENOUS AND ORAL ADMINISTRATION OF RACEMIC VERAPAMIL IN A RAT MODEL

Verapamil is a chiral calcium channel blocking drug which is useful clinically as the racemate in treating hypertension and arrhythmia. The published pharmacokinetic data for verapamil enantiomers in the rat model are limited. Utilizing a stereospecific high‐performance liquid chromatographic (HPLC)...

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Bibliographic Details
Published in:Biopharmaceutics & drug disposition 1997-07, Vol.18 (5), p.387-396
Main Authors: BHATTI, M. MASOOD, FOSTER, ROBERT T.
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Area Under Curve
bioavailability
Biological and medical sciences
Calcium Channel Blockers - pharmacokinetics
Cardiovascular system
Chromatography, High Pressure Liquid
Injections, Intravenous
Male
Medical sciences
Miscellaneous
pharmacokinetics
Pharmacology. Drug treatments
rat
Rats
Rats, Sprague-Dawley
Stereoisomerism
Verapamil - pharmacokinetics
verapamil enantiomers
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Summary:Verapamil is a chiral calcium channel blocking drug which is useful clinically as the racemate in treating hypertension and arrhythmia. The published pharmacokinetic data for verapamil enantiomers in the rat model are limited. Utilizing a stereospecific high‐performance liquid chromatographic (HPLC) assay, the enantiomeric disposition of verapamil is reported after intravenous (1·0 mg kg−1) and oral (10 mg kg−1) administration of racemic verapamil to the rat model. After intravenous administration the systemic clearance of R‐verapamil was significantly greater than that of S‐verapamil; 34·9 ± 7  against 2·7 ± 3·7 mL min−1 kg−1 (mean ± SD), respectively. After oral administration, the clearance of R‐verapamil was significantly greater than that of S‐verapamil, 889 ± 294  against 351 ± 109 mL min−1 kg−1, respectively. The apparent oral bioavailability of S‐verapamil was greater than that of R‐verapamil, 0·074 ± 0·031 against 0·041 ± 0·011, respectively. These data suggest that the disposition of verapamil in the rat is stereoselective; verapamil undergoes extensive stereoselective first‐pass clearance after oral administration and the direction of stereoselectivity in plasma is opposite to that observed in the human. © 1997 John Wiley & Sons, Ltd.
ISSN:0142-2782
1099-081X
DOI:10.1002/(SICI)1099-081X(199707)18:5<387::AID-BDD26>3.0.CO;2-X