OXAZEPAM DISPOSITION IN UREMIC PATIENTS

Abstract

The pharmacokinetics of oxazepam was investigated in 13 uremic patients. The apparent terminal half-life of oxazepam in plasma was 24-91 h compared to 5.9-25 h reported elsewhere for healthy volunteers. The plasma concentrations showed secondary peaks about 24 h after the dose and this probably gave rise to the increase in half-life. Plasma clearance of oxazepam appeared to be normal. The conjugated metabolites accumulated to concentrations 5-50 times those of the parent compound and could still be detected 5 days after a single oral dose (0.2 mg/kg). Renal clearance of conjugated oxazepam was significantly correlated to creatinine clearance. The urinary recovery over 5 days was 18-57%. The fecal recovery over 3 days was 0.1-19%. In some patients up to 49% of oxazepam in feces was in the conjugated form. Enterohepatic recycling of oxazepam might occur in uremic patients but is not of great quantitative importance. During multiple dosing the accumulation of conjugates was even more pronounced, with plasma concentrations amounting to 14-61 times those of oxazepam. Steady-state plasma concentrations of oxazepam were similar to those obtained in normal subjects.