Pharmacokinetics of the peripheral benzodiazepine receptor antagonist, PK 11195, in rats. The effect of dose and gender.

In spite of the extensive use of the peripheral benzodiazepine (BZ) receptor antagonist, PK 11195 (PK), in pharmacological studies, there is a lack of information of its pharmacokinetics in the rat. In this study the pharmacokinetics of PK were determined after bolus intravenous (i.v.) administration in rat. The effects of dose and gender were evaluated in Sprague-Dawley age-matched male and female rats after the injection of PK (5, 10, 20 mg kg(-1)). Plasma was collected at 5-300 min. Levels of PK in plasma and brain were determined by a novel HPLC method. The stability of PK in blood in vitro was determined. PK is stable in rat blood in vitro. The pharmacokinetics of PK are described by a two-compartment model. The half-lives for distribution ( approximately 0.14 h) and elimination ( approximately 5.4 h) are not related to dose. The large volume of distribution (9-24 l kg(-1)) indicates an extensive distribution outside plasma. Total plasma clearance increases with increasing dose (23-42 ml min(-1)kg(-1)). The brain/plasma ratio ( approximately 3) is not related to dose. These finding suggest that the pharmacokinetics of PK are related to dose (5-20 mg kg(-1)) and gender in rat. Copyright 2000 Academic Press.