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 (Varea) than did younger subjects (1.96 vs. 1.63 L/kg; P less than 0.05); because clearance did not change with age (0.84 vs. 0.95 ml/min/kg), the prolonged t1/2 in elderly men (28 vs. 20 hours; P less than 0.01) was a result of the larger Varea. Elderly and young women did not differ in nitrazepam Varea (2.58 vs. 2.55 L/kg), t1/2 (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.
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000375:Aging; D000983:Antipyrine / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D002849:Chromatography, Gas; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009567:Nitrazepam / Q000097:blood / Q000378:metabolism*; D011485:Protein Binding; D012737:Sex Factors
D001798:Blood Proteins; D009567:Nitrazepam; D000983:Antipyrine