Disposition and metabolism of [14C]loperamide in rats
| Autor: | Keiko Nambu, Yoshimasa Matsunaga, Hisashi Miyazaki, Masahisa Hashimoto |
|---|---|
| Rok vydání: | 1979 |
| Předmět: |
Male
medicine.medical_specialty Loperamide Time Factors Clinical chemistry Urine In Vitro Techniques Pharmacology Loperamide Hydrochloride Feces Piperidines Oral administration Internal medicine medicine Animals Bile Pharmacology (medical) Carbon Radioisotopes Biotransformation Demethylation Chemistry Metabolism Rats Endocrinology Intestinal Absorption Liver Protein Binding medicine.drug |
| Zdroj: | European Journal of Drug Metabolism and Pharmacokinetics. 4:199-206 |
| ISSN: | 2107-0180 0378-7966 |
| DOI: | 10.1007/bf03189427 |
| Popis: | Following oral administration of [14C]loperamide hydrochloride in 1 mg/kg to rats, plasma levels of radioactivity reached maximum at 4 hrs and decreased with a half-life of 4.1 hrs. Radioactivity in 96-hr feces accounted for 95% of the dose, with 30% associated with unchanged drug, while that in urine only 3.5%. Radioactivity in 48-hr bile accounted for 42% of the dose associated entirely with metabolites. 3% of the dose was found at the level of the enterohepatic cycles. These findings show that about 70% of the dose with absorbed by intestine, the target tissue of the drug, a portion (30%) of which was excreted back into intestinal cavity after demethylation, while the remaining 40% transferred to liver by which it was extracted mostly, metabolized extensively and excreted largely into bile, as supported by in vitro demethylating activity in gut segments but none in gut contents, and by in situ marked hepatic extraction of the drug. Main metabolic pathways involved are described. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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