Enantioselective Pharmacokinetics of Homochlorcyclizine: Disposition of (+)- and (–)-Homochlorcyclizine after Intravenous and Oral Administration of Racemic Homochlorcyclizine to Rats
| Autor: | Katsumi Miyazaki, Keishiro Miyake, Aki Nakai, Hitomi Fushida, Takaichi Arita, Mayumi Nishikata, Ken Iseki |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Erythrocytes Administration Oral Pharmaceutical Science Absorption (skin) In Vitro Techniques Pharmacology Kidney High-performance liquid chromatography Rats Sprague-Dawley Pharmacokinetics Homochlorcyclizine Oral administration medicine Animals Bile Cyclizine Tissue Distribution Intestinal Mucosa Lung Chromatography High Pressure Liquid Chemistry Myocardium Brain Stereoisomerism Blood Proteins Metabolism Rats medicine.anatomical_structure Intestinal Absorption Liver Gastric Mucosa Injections Intravenous Histamine H1 Antagonists Enantiomer Spleen Protein Binding medicine.drug |
| Zdroj: | Journal of Pharmacy and Pharmacology. 46:591-595 |
| ISSN: | 2042-7158 0022-3573 |
| DOI: | 10.1111/j.2042-7158.1994.tb03863.x |
| Popis: | Concentrations of homochlorcyclizine enantiomers in blood, urine, and tissues of the liver, lung, kidney, brain, heart, spleen, intestine and stomach of rats after drug administration were determined by high-performance liquid chromatography on a chiral stationary phase. After intravenous administration (10 mg kg−1), homochlorcyclizine was rapidly distributed in many tissues, with the highest concentration in lung. No differences were found between enantiomers in blood concentrations. After oral administration (50 mg kg−1), the concentrations of the (+)-isomer in nearly all tissues were higher than those of the (–)-isomer. The AUC0-x values of the (+)- and (–)-isomers differed significantly. The absorption of racemic homochlorcyclizine from rat small intestine was not enantioselective. These results suggested that the different concentrations between enantiomers after oral administration were not caused by enantioselective absorption or distribution but rather by preferential first-pass metabolism of the (–)-isomer in the liver. The enantioselectivity of metabolism was also demonstrated by in-vitro experiments. |
| Databáze: | OpenAIRE |
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