Pharmacokinetics and metabolism of a selective PDE5 inhibitor (UK-343,664) in rat and dog

Abstract

1. UK-343,664 is a novel potent and selective PDE5 inhibitor. Plasma clearances in the male and female rat were high (120 and 54 ml min^-1 kg^-1), giving rise to short elimination half-lives (0.2 and 0.3 h respectively). Lower clearance in dog (14 mlmin^-1 kg^-1) was the primary factor resulting in a longer elimination half-life (3.7 h). The higher clearance in rat than dog was in agreement with in vitro metabolism rates in hepatic microsomes. 2. The volume of distribution was lower in rat (1.3-2.1 lkg^-1) compared with dog (4.6 l kg^-1