Abstract
Pharmacokinetics and metabolism of diltiazem and a new analogue, LR-A/113, have been studied in the rat Conscious rats, with the jugular vein cannulated, received the compounds by intravenous (3 mg/kg body weight) or oral (50 mg/kg body weight) route. Parent compounds and their N-demethyl and N-deacetyl metabolites were assayed at serial times in blood. Half-life of elimination of diltiazem was significantly shorter than that of LR-A/113, both after oral (37±9 vs 59±26 min) and intravenous (29±12 vs 57±16 min) administration. N-deacetyl-diltiazem concentrations after oral administration were higher than the parent compound and N-demethyldiltiazem; LR-A/113 blood concentrations were higher than those of its two metabolites. Metabolites were measurable only in traces after intravenous administration. Oral bioavailability was very low, 3.5% for diltiazem and 4.2% for LR-A/113. In conclusion, the substitution of a methyl by an isopropyl group appears to slow in vivo elimination of the analogue of diltiazem, LR-A/113.
Original language | English |
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Pages (from-to) | 269-274 |
Number of pages | 6 |
Journal | European Journal of Drug Metabolism and Pharmacokinetics |
Volume | 17 |
Issue number | 4 |
DOIs | |
Publication status | Published - Oct 1992 |
Keywords
- Calcium antagonist
- diltiazem
- metabolism
- pharmacokinetics
- rat
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
- Pharmacology, Toxicology and Pharmaceutics(all)