Metabolism and disposition of (R)-4-[3-(2-hydroxy-2-phenyl)ethylamino-3-methylbutyl]benzamide Hcl (LY 195448) in rodents

Res Commun Chem Pathol Pharmacol. 1989 Nov;66(2):255-67.

Abstract

The disposition and metabolism of (R)-4-[3-(2-hydroxy-2-phenyl)ethylamino-3-methylbutyl]benzamide HCl, or LY 195448 (LY), were studied in rodents 1 hr following a single iv injection of 14C-LY at 30 mg/m2 (10 mg/kg mice and 5 mg/kg rats), In all tissues and carcases, recovery of 14C was nearly complete. The majority of radioactivity was recovered from intestine (40%) whereas liver and urine accounted for 10% each, kidney for 3-5%, and plasma for 1-3% of total administered radioactivity. Analyzing by HPLC and TLC, para-hydroxy-LY (para-OH-LY) in addition to unchanged drug, was found in all tissues. Meta-OH-LY was detected only in urine, intestine and kidney. These metabolites were found to be conjugated with either glucuronide or sulfate moieties. Peaks coeluting with authentic para-OH-meta-methoxy-LY and di-OH-LY were also observed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / pharmacokinetics
  • Benzamides / metabolism*
  • Benzamides / pharmacokinetics
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Dogs
  • Ethanolamines / metabolism*
  • Ethanolamines / pharmacokinetics
  • Female
  • Glucuronidase / metabolism
  • Humans
  • Hydrolysis
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Microsomes, Liver / metabolism
  • Multienzyme Complexes / metabolism
  • Rats
  • Rats, Inbred Strains
  • Sulfatases / metabolism
  • Tissue Distribution

Substances

  • Antineoplastic Agents
  • Benzamides
  • Ethanolamines
  • Multienzyme Complexes
  • glusulase
  • 4-(3-(2-hydroxy-2-phenyl)ethylamino-3-methylbutyl)benzamide
  • Sulfatases
  • Glucuronidase