Abstract
Ed 7–14 days after each dose. After intravenous injection, diazepam volume of distribution (Vd) was larger in women than in men, but increased with age regardless of sex. Elimination half-life was longer in elderly than in young men (101 v 32 h, P < 0.025), partly due to the increased Vd as well as to a significant reduction in total metabolic clearance (0.24 v 0.46 ml/min/kg, P < 0.05). However, the prolonged half-life in elderly as opposed to young women (99 v 44 h; P < .01) was due mainly to increased Vd because clearance was not significantly changed (0.29 v 0.35 mil ml/min/kg). In all subjects, oral diazepam was rapidly absorbed; peak plasma levels were reached an average of 0.9 h after dosage. Absolute bioavailability averaged 94%, indicating essentially complete absorption. Neither age nor sex significantly influenced oral absorption. In all male subjects, and in 8 of 12 women, absorption of diazepam after deltoid intramuscular injection was rapid and essentially complete. However, in three young and one elderly women, absorption was slower and apparently incomplete. Age as such did not significantly influence absorption of intramuscular diazepam. Reprint requests to Dr. Greenblatt, Division of Clinical Pharmacology, Box 1007, New England Medical Center Hospital, 171 Harrison Avenue, Boston, MA 02111. This study was supported in part by Grant MH-34223 from the United States Public Health Service and by Grant Oc 10/6–3 from Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg, West Germany. Accepted for publication July 13, 1982. © 1983 International Anesthesia Research Society...