Pharmacokinetics and metabolism of a novel antifibrotic drug pirfenidone, in mice following intravenous administration

Shri N. Giri, Qingjian Wang, Yan Xie, Jozsef Lango, Dexter Morin, Solomon B. Margolin, Alan R Buckpitt

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


The present study describes the pharmacokinetics and metabolism of pirfenidone (PD), a compound which has been shown to have significant antifibrotic effects in rodent models of pulmonary and cardiac fibrosis. Despite the fact that this compound is currently in phase II clinical trials, little data are available on the metabolism and disposition of this agent in rodents or humans. Radioactive PD [benzene ring 14C(U)] was administered i.v. to mice at 40 mg PD/kg body weight, and animals were killed at varying times for determination of parent compound and metabolites in various tissues. The disappearance of parent compound from the plasma followed apparent 2-compartment elimination kinetics with a terminal elimination half-life of 8.6 min. Cl (0.10 ml/min/g) and Vd(ss) (0.67 ml/g) indicated that PD was rapidly distributed in body water. This is consistent with the finding that peak tissue radioactivity occurred within 5 min following the i.v. administration of [14C]-PD and that well-perfused tissues, kidney>liver>lung have much higher levels of parent compound and metabolites than did fat. Two peaks isolated from plasma samples by HPLC yielded mass spectra that were consistent with initial oxidation to the alcohol followed by further metabolism to the carboxylic acid. The radioactivity recovered in the 24 h urine samples averaged 97% of the administered dose and none of that was associated with the parent compound. The short plasma half-life of parent compound in mice supports the need for additional studies in humans where the compound has been shown to have clinical benefits.

Original languageEnglish (US)
Pages (from-to)203-211
Number of pages9
JournalBiopharmaceutics and Drug Disposition
Issue number5
StatePublished - Jul 2002


  • Antifibrotic drug
  • Metabolism
  • Pharmacokinetics
  • Pirfenidone

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)


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