Anesthesia & Analgesia

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Anesthesia & Analgesia:

Absolute Bioavailability of Oral and Intramuscular Diazepam: Effects of Age and Sex.

Divoll, Marcia BS; Greenblatt, David J. MD; Ochs, Hermann R. MD; Shader, Richard I. MD

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Twenty-two healthy volunteers aged 20-78 years received single 5-mg doses of diazepam by intravenous injection, by mouth in the fasting state, and by a deltoid intramuscular injection. The kinetic profile of diazepam by each route was determined from multiple plasma diazepam concentrations measured 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.

(C) 1983 International Anesthesia Research Society


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