Renal disease, age, and oxazepam kinetics

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Abstract
Effects of renal insufficiency and age on oxazepam kinetics were assessed in 13 normal subjects (21-72 yr old), 4 patients with renal insufficiency and 8 patients on hemodialysis. Normal intact oxazepam results were: mean elimination half-life (t1/2), 10 h; area under the curve (AUC), 6.0 .mu.g .cntdot. h/ml; unbound oxazepam fraction (fup), 3.2%; maximum concentration of unbound oxazepam (Cmax,u), 16 ng/ml; and intrinsic (unbound drug) clearance (Clint), 2.9 l/h per kg. Less than 1% of the dose was excreted intact in urine. Age differences had no influence on results. In renal insufficiency patients, t1/2 was prolonged to 25 h, fup increased to 7%, and Cmax,u and Clint were unchanged. Volume of distribution of unbound oxazepam (Vu) increased, prolonging t1/2. In dialysis patients, t1/2 was prolonged to 33 h, fup increased to 6.2%, and Cmax,u and Clint again were unchanged. Oxazepam was undialyzable; since unbound oxazepam disposition kinetics are not altered, no dosage adjustment is necessary. Oxazepam is a benzodiazepine sedative-tranquilizer.

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