PMID: 8584501Aug 1, 1995Paper

Metabolism is an important route of pentamidine elimination in the rat: disposition of 14C-pentamidine and identification of metabolites in urine using liquid chromatography-tandem mass spectrometry

Pharmacology & Toxicology
U BronnerL L Gustafsson

Abstract

This study assesses the contribution of metabolism for the disposition of pentamidine in the rat. With the use of 14C-labelled compound, the excretion of radioactivity in urine and faeces has been studied in four rats during 44 days after a single intravenous injection of the drug. The urinary and faecal excretion of the radioactivity were of equal importance; 22 +/- 2% (mean +/- S.D.) and 25 +/- 4% being detected in urine and faeces, respectively. The activity in organs and tissues at 44 days after drug administration was also measured and amounted to 21 +/- 5% of the administered dose. Using HPLC the proportion of metabolites in urine in relation to unchanged pentamidine increased with time after dose, being 76 +/- 15% (mean +/- S.D.) of the total excreted radioactivity on day 1 and 97 +/- 1% on day 6. HPLC--tandem mass spectometry was used for identification of metabolites in urine obtained from four rats given unlabelled pentamidine. Using synthetic reference compounds and the selective MS/MS mode four oxidized metabolites of pentamidine were identified either by direct injection into the system or by analyses of extracted urine. Thus, a substantial part of pentamidine is excreted as metabolites in urine.

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Citations

Aug 13, 1998·Journal of Chromatography. B, Biomedical Sciences and Applications·H H Maurer
May 26, 2011·Malaria Journal·Jane AchanUmberto D'Alessandro
Mar 19, 2008·Basic & Clinical Pharmacology & Toxicology·Anja BürenheideBernd Clement
Oct 31, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Xin MingDhiren R Thakker
Mar 28, 1998·Antimicrobial Agents and Chemotherapy·J E HallR R Tidwell

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