The pharmacokinetics of pirtenidine in the rat and dog

Xenobiotica. 1989 Dec;19(12):1349-54. doi: 10.3109/00498258909043186.

Abstract

1. Pharmacokinetic studies on the topical antimicrobial agent, pirtenidine, have been conducted in male Sprague-Dawley rats and beagle dogs, using a validated h.p.l.c. method with u.v. detection to measure the drug in plasma. 2. Following a single i.v. bolus dose to the rat (equivalent to 1.35 mg base/kg) or dog (equivalent to 0.23 mg base/kg), the drug was extensively distributed with an apparent volume of distribution of 8.61/kg in rat and 3.31/kg in dog. Clearance was high (rat 2.71/h/kg; dog 1.51/kg) which resulted in a short terminal half-life in both species (2.2 and 1.5 h respectively). 3. Following a single oral dose to rats (equivalent to 4.5 mg base/kg) plasma pirtenidine concentrations were generally below the minimum quantifiable level of the analytical method (1 ng/ml). A maximum possible bioavailability of 0.3% was estimated. 4. After administering the same oral dose to dogs plasma concentrations rose slowly (t 1/2 abs = 1.2 h) to a peak (49.7 ng/ml) at 5.0 h post-dose. The terminal elimination half-life was 2.1 h. The absolute bioavailability was 10%.

MeSH terms

  • Aminopyridines / pharmacokinetics*
  • Aminopyridines / toxicity
  • Animals
  • Anti-Infective Agents / pharmacokinetics*
  • Anti-Infective Agents / toxicity
  • Dogs
  • Half-Life
  • Male
  • Rats
  • Rats, Inbred Strains
  • Species Specificity

Substances

  • Aminopyridines
  • Anti-Infective Agents
  • pirtenidine