Age, sex, and nitrazepam kinetics: Relation to antipyrine disposition

Forty healthy men and women 19 to 80 years old received a single 10 mg oral dose of the 7‐nitro benzodiazepine nitrazepam. Nitrazepam plasma concentrations were measured during the next 72 hours. Among men, the elderly had a larger volume of distribution (V area ) than did younger subjects (1.96 vs. 1.63 L/kg; P < 0.05); because clearance did not change with age (0.84 vs. 0.95 ml/min/kg), the prolonged t ½ in elderly men (28 vs. 20 hours; P < 0.01) was a result of the larger V area . Elderly and young women did not differ in nitrazepam V area (2.58 vs. 2.55 L/kg), t ½ (26 vs. 27 hours), or total clearance (1.19 vs. 1.09 ml/min/kg). The nitrazepam free fraction in plasma (18% to 19% unbound) was not related to age or sex. Among 18 subjects who also received antipyrine, the clearance of nitrazepam and antipyrine were not correlated (r = 0.23). Thus age minimally influences nitrazepam clearance (accomplished mainly by nitroreduction), which in turn is not significantly related to antipyrine oxidizing capacity. Clinical Pharmacology and Therapeutics (1985) 38 , 697–703; doi: 10.1038/clpt.1985.248