The metabolism of (2-cyclopentyl-6,7-dichloro-2-methyl-1-oxo-5-indanyloxy)acetic acid in chimpanzee and man

Drug Metab Dispos. 1978 May-Jun;6(3):303-12.

Abstract

The metabolism of the polyvalent saluretic agent (2-cyclopentyl-6,7-dichloro-2-methyl-1-oxo-5-indanyloxy)acetic acid was studied in chimpanzee and man. The drug was well absorbed and extensively metabolized by man. Peak levels of drug (5--8 microgram/ml) occurred within 1.5--4.5 hr of drug administration. The plasma half-life was estimated to be 2 hr; a similar half-life was observed in the chimpanzee. Little unchanged drug (less than 10%) was excreted in the urine of either species. Similar metabolic profiles were obtained for man and chimpanzee. The major urinary metabolites resulted from hydroxylation of the cyclopentyl moiety, giving rise to a number of diastereomers. The alcohol metabolites were subsequently oxidized to the ketone. The excretion of the metabolites coincided with maximal excretion of sodium and chloride ions. The hydroxylated metabolites have intrinsic pharmacological activity.

MeSH terms

  • Animals
  • Chlorides / urine
  • Chromatography, Gas
  • Chromatography, Thin Layer
  • Diuretics / metabolism*
  • Glycolates / metabolism*
  • Humans
  • Indans / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Mass Spectrometry
  • Pan troglodytes
  • Sodium / urine
  • Time Factors

Substances

  • Chlorides
  • Diuretics
  • Glycolates
  • Indans
  • Sodium