The kinetics of single 30-mg oral doses of oxazepam were determined in 22 male and nine female volunteers aged 20-86 years. Oxazepam plasma concentrations were measured in multiple plasma samples drawn during 36 h after each dose. Mean kinetic variables in males and females, respectively, were: elimination half-life, 7.5 and 8.5 h; volume of distribution, 0.96 and 1.17 l/kg; clearance, 1.48 and 1.70 ml/min/kg. Sex differences were not significant, nor were any of the kinetic variables significantly related to age. However, oxazepam clearance increased significantly with heavier cigarette smoking (r = 0.48, p less than 0.01). Mean clearance in smokers (1.98 ml/min/kg) was significantly higher than in nonsmokers (1.23 ml/min/kg, p less than 0.01). Thus, smoking is a more important determinant of oxazepam clearance than age or sex.

1 Eight patients with end‐stage renal insufficiency on maintenance haemodialysis, and seven patients with newly diagnosed hyperthyroidism, received a single intravenous dose of diazepam, followed by blood sampling over the next 7 days. Fifteen healthy volunteer controls, matched with patients for age and sex, were similarly studied. 2 Diazepam half‐life in renal failure patients (mean 37 h) was greatly reduced compared to controls (mean 92 h, P less than 0.05) and clearance of total (free plus bound) diazepam correspondingly increased (0.94 v 0.34 ml min‐1 kg‐1, P less than 0.01). 3 However, differences were largely related to disease‐related changes in drug binding and distribution. Mean unbound fraction of diazepam in plasma of renal patients (7.0%) was greatly increased over controls (1.4%, P less than 0.01) and Vd of unbound diazepam greatly reduced (57 v 157 l/kg, P less than 0.01). 4 Clearance of pharmacologically active unbound diazepam (intrinsic clearance) was not significantly different between renal patients and controls (23 vs 30 ml min‐1 kg‐1). 5 None of the kinetic variables for total or unbound diazepam in thyrotoxic patients differed significantly from those in controls matched for age and sex. 6 End‐ stage renal failure (or its associated drug therapy) alters diazepam protein binding and distribution, but does not significantly change clearance of unbound drug. Thyrotoxicosis does not influence diazepam kinetics.

Healthy volunteers received a single dose of triazolam (0.5 mg) or oxazepam (30 mg) on two occasions, once in the control state and again during coadministration of isoniazid (INH) base, 180 mg day. INH coadministration prolonged triazolam half-life (3.3 vs 2.5 h, P < 0.05) and increased total area under the curve (38.6 vs 26.5 ng ml-' h, P < 0.01) consistent with a reduction of apparent oral clearance (3.9 vs 6.8 ml minm 'kg-', 0.05 < P < 0.1). INH coadministration had no influence on the kinetics of oxazepam. INH impairs hepatic microsomal oxidation of triazolam, leading to reduced first-pass hepatic extraction as well as prolonged half-life. However INH had no influence on oxazepam conjugation.

1 Nitrazepam pharmacokinetics were studied in 14 obese (mean ± s.e. mean body weight 107 ± 9 kg; percent ideal body weight [IBW] .6 ng ml-1; NS) and time required after drug administration to reach peak concentration (1.52 ± 0.24-obese vs 1.59 ± 0.36 h; NS) indicated no differences between obese and control subjects.3 Elimination half-life was markedly increased in obese subjects (33.5 ± 2.2 vs 23.9 + 1.2 h; P < 0.001) due to increased apparent volume of distribution (Vd) (290 ± 45 vs 137 + 12 l; P < 0.005). Oral clearance was also increased in the obese subjects (101 ± 12.4 vs 66.8 ± 12.4 ml min-'; P < 0.02). Extent of nitrazepam binding to plasma proteins was slightly decreased in obese subjects (% unbound-19.7 ± 0.4-obese vs 17.9 ± 0.3%; P < 0.005). 4 Correction of both Vd(2.62 ± 0.17-obese vs 2.22 ± 0.19 1kg-1; NS) and clearance (0.93 ± 0.06-obese ± 1.07 ± 0.07 ml min-' kg-1; NS) for total body weight (TBW) suggested that increases in obese subjects of both of these parameters were a function of body weight. Total Vd and percent IBW were highly correlated across subject groups (r = 0.87; P < 0.001) as were clearance and percent IBW (r = 0.77; P < 0.001). 5 Although clinical correlations are not established, unchanged absorption parameters between control and obese groups suggest no need for nitrazepam dose adjustment for obese insomniacs with difficulty falling asleep.

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