Hepatic and extrahepatic glucuronidation of lorazepam in the dog.

Abstract

The pharmacokinetic disposition of lorazepam was investigated in sham-operated aneshetized dogs, dogs with hepatic devascularization, and dogs with total splanchnic devascularization following i.v. administration of 0.3 mg per kg of the drug. In sham-operated dogs, lorazepam distribution was extensive (100 +/- 15.2 liters) and clearance approximately expected liver blood flow (971 +/- 91 ml per min). Lorazepam glucuronide levels in plasma rose rapidly in the first hour and reached a plateau by 5 hr. Urinary recovery of the conjugate in 5 hr was 45% of administered dose. Hepatic devascularization resulted in 39% reduction in distribution volume, and 89% reduction in clearance; however, there ..