Browse > Article

Pharmacokinetic Behavior and Tissue Distribution of Verapamil and Its Enantiomers in Rats by HPLC  

He, Langchong (College of Pharmacy, Xi an Jiaotong University)
Wang, Sicen (College of Pharmacy, Xi an Jiaotong University)
Publication Information
Archives of Pharmacal Research / v.26, no.9, 2003 , pp. 763-767 More about this Journal
Abstract
The differences in pharmacokinetic behavior and tissue distribution of verapamil and its enantiomers were investigated in rats. In high-performance liquid chromatographic method, an achiral ODS column (150 mm $\times$ 4.6 mm i.d.) with the mobile phase consisting of methanol-water (73:30, v/v) was used for the determination of the concentration for racemic verapamil, and a Chiralcel OJ column (250 mm$\times$4.6 mm i.d.) with the mixture of n-haxane-ethanol-triethylamine (85:15:0.2, v/v/v) as mobile phase was used to determine the concentrations of verapamil enantiomers. A fluorescence detector in the analytical system was set at excitation and emission wavelengths of 275 nm and 315 nm. The differences between enantiomers were apparent in the pharmacokinetics in rats. The area under the concentration-time curve (AUC) of S-(-) verapamil was higher than that of R-(+) verapamil. The half-distribution time ($T_{1/2(\alpha)}$) of S-(-) verapamil which distributing to tissue from blood was shorter than that of R-(+) verapamil, but the elimination half-time ($T_{1/2(\beta)}$) was longer in rat following oral administration of racemic verapamil. At 1.3 h after oral administration of racemic verapamil, however, there were no significant differences between enantiomers for the distributions in major tissues such as heart, cerebrum, cerebellum, liver, spleen and kidney.
Keywords
Verapamil; Enantiomer separation; Pharmacokinetics; Tissues distribution;
Citations & Related Records

Times Cited By Web Of Science : 0  (Related Records In Web of Science)
Times Cited By SCOPUS : 0
연도 인용수 순위
  • Reference
1 Amsterdam, F. T. and Zaagsma, J., Nauny Schmiedebergs Arch. Pharmacol., 337, 213-219 (1988)   DOI
2 Asafu-Adjaye, E. B. and Gerald, K. Shiu, Solid-phase extraction high-performance liquid chromatography determination of verapamil and norverapamil enantiomers in urine. J. Chromatogr. B, 707, 161-167 (1998)   DOI   ScienceOn
3 Grazia Stagni, William, R., and Gillespie, Simultaneous analysis of verapamil and norverapamil enantiomers in human plasma by high-performance liquid chromatography. J. Chromatogr. B, 667, 349-354 (1995)   DOI   ScienceOn
4 Satoh, K., Yanagisawa, T., and Taira, N., Coronary vasodilator and cardiac effects of optical isomers of verapamil in the dog. J. Cardiovasc. Pharmacol., 2, 309 (1980)   DOI   PUBMED   ScienceOn
5 Echizen, H., Manz, M., and Eichelbaus, M., Electrophysiologic effects of dextro- and levo-verapamil on sinus nod and AV mode function in humans. J. Cardiovasc. Pharmacol., 12, 543 (1988)   DOI   PUBMED   ScienceOn
6 Brandsteterova, E. and Wainer, I. W., Achiral and chiral highperformance liquid chromatography of verapamil and its metabolites in serum samples. J. Chromatogr. B, 732, 395-404 (1999)   DOI   ScienceOn
7 Triggle, D. J., Calcium Channel Drugs: Antagonists and Activators. ISI Atlas Pharmacol., 1, 319-324 (1987)
8 Ho-Sang Shin, Yun-Suk Oh-Shin, and Hyun-Jin Kin, et al., Sensitive assay for verapamil in plasma using gas-liquid chromatography with nitrogen-phosphorus detection. J. Chromatogr. B, 677, 369-373 (1996)   DOI   ScienceOn
9 Sandsteom, R., Lennernas, H., and Ohlen, K., et al., Enantiomeric separation of verapamil and norverapamil using chiral-AGP as the stationary phase. J. Pharm. Biomed. Anal., 21, 43-49 (1992)
10 Hanada, K., Akimoto, S., Mitsui, K., Hashiguchi, M., and Ogata, H., Quantitative determination of disopyramide, verapamil and flecainide enantiomers in rat plasma and tissues by highperformance liquid chromatography. J. Chromatogr. B, 710, 129-135 (1998)   DOI   ScienceOn