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

Eur J Drug Metab Pharmacokinet. Oct-Dec 1992;17(4):269-74. doi: 10.1007/BF03190159.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Consciousness
  • Diltiazem / analogs & derivatives*
  • Diltiazem / pharmacokinetics*
  • Half-Life
  • Male
  • Rats
  • Rats, Sprague-Dawley

Substances

  • siratiazem
  • Diltiazem