Quazepam kinetics in the elderly

The kinetics of quazepam, a benzodiazepine hypnotic, was studied in 10 geriatric subjects. Each received one 15‐mg tablet of quazepam. Blood samples were collected before and at specified times (up to 672 hr) after dosing. Plasma concentrations of quazepam and its two major active plasma metabolites, 2‐oxoquazepam and N‐desalkyl‐2‐oxoquazepam (N‐desalkylflurazepam), were determined by specific GLC methods. Kinetics were best described by a two‐compartment open model with first‐order absorption/formation kinetics and standard equations. Quazepam was rapidly absorbed, with a t½ of 0.8 hr. The mean maximum plasma level (C max ) was 29.3 ng/ml. The disposition t½s in the distribution (t½α) and elimination (t½β) phases were 3.5 and 53.3 hr. 2‐Oxoquazepam was rapidly formed with quazepam, with an apparent formation t½ of 0.8 hr. Mean C max was 14.5 ng/ml. The t½α and t½β of 2‐oxoquazepam were 4.2 and 43.1 hr, of the order of those of quazepam. The t½β of N‐desalkyl‐2‐oxoquazepam, formed from 2‐oxoquazepam, was 189.7 hr, much longer than that of its precursor. Comparison of these data with reported kinetic data in young subjects shows that t½βs of quazepam and 2‐oxoquazepam increased only slightly or not at all with age, but that the t½β of N‐desalkyl‐2‐oxoquazepam in the elderly was more than twice that in young subjects. Clinical Pharmacology and Therapeutics (1984) 36, 566–569; doi: 10.1038/clpt.1984.220