Pharmacokinetics of diltiazem and a new analogue, LR-A/113, in the conscious rat

R. Bernasconi, S. Caliari, R. Latini, D. Leopaldi, S. Porzio, A. Salimbeni

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)269-274
Number of pages6
JournalEuropean Journal of Drug Metabolism and Pharmacokinetics
Volume17
Issue number4
DOIs
Publication statusPublished - Oct 1992

Keywords

  • Calcium antagonist
  • diltiazem
  • metabolism
  • pharmacokinetics
  • rat

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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