Renal disease, age, and oxazepam kinetics

Effects of renal insufficiency and age on oxazepam kinetics were assessed in 13 normal subjects (21 to 72 yr old), four patients with renal insufficiency, and eight patients on hemodialysis. Normal intact oxazepam results were: mean elimination half-life (t1/2), 10 hr; area under the curve (AUC), 6.0 microgram.hr/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/hr/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 hr, fup increased to 7%, and Cmax,u and Clint were unchanged. Volume of distribution of unbound oxazepam (Vu) increased, thereby prolonging t1/2. In dialysis patients, t1/2 was prolonged to 33 hr, 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 for patients is necessary.