Pharmacokinetic study of benidipine hydrochloride in rats and dogs

Arzneimittelforschung. 1988 Nov;38(11A):1750-3.

Abstract

(+/-) - (R*) - 2,6-Dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine - 3, 5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) is presently under development as an anti-hypertensive and antianginal agent. A pharmacokinetic study in rat and dog after oral and intravenous administrations revealed that KW-3049 was rapidly absorbed from the gastrointestinal tract, distributed into tissues moderately and comparatively quickly eliminated. After oral administration, non-linearity of bioavailability with increment of doses was observed in both rat and dog. Female and male rats showed similar drug disposition after intravenous administration. Oxidation product of KW-3049 dihydropyridine ring was also measured in some plasma samples. The concentration rates of its pyridine metabolite accounted for 0 to 30% and 0 to 23% of the combined concentration of KW-3049 plus the pyridine metabolite in rat and dog.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / pharmacokinetics*
  • Calcium Channel Blockers / toxicity
  • Dogs
  • Female
  • Half-Life
  • Injections, Intravenous
  • Intestinal Absorption
  • Male
  • Nifedipine / administration & dosage
  • Nifedipine / analogs & derivatives*
  • Nifedipine / pharmacokinetics
  • Nifedipine / toxicity
  • Oxidation-Reduction
  • Rats
  • Rats, Inbred Strains
  • Tissue Distribution

Substances

  • Calcium Channel Blockers
  • benidipine hydrochloride
  • Nifedipine