Pharmacokinetics of oxazepam following multiple administration in volunteers and patients with chronic renal disease.

The plasma level course and the elimination of oxazepam (Adumbran) via urine were investigated following multiple oral administration in volunteers and patients with chronic renal failure. Additionally, drug metabolizing enzyme systems had been induced in the volunteers by pretreatment with phenobarbital. The plasma protein binding in vitro of oxazepam was determined in volunteers and patients. The plasma levels and the renal elimination of oxazepam and its metabolites do not show any differences between the two groups of volunteers (oxazepam and oxazepam after pretreatment). 83--92% of the dosage are eliminated via urine. In comparison, the plasma levels of oxazepam in patients with renal failure are half those of the volunteers. However, the plasma levels of oxazepam metabolites in patients are much higher than in volunteers and these increases correlate to the creatinine clearance of the patients. The non-protein bound oxazepam in plasma was found to be twice as high in the plasma of patients as that of volunteers. As a consequence, the lower plasma level of oxazepam in patients will be compensated for so that the pharmacological activity in patients and volunteers due to free oxazepam in the plasma water is nearly the same. Therefore a new dosage regimen for treatment with oxazepam in patients with renal failure is not necessary.