Pharmacokinetics of oral brotizolam in patients with liver cirrhosis.

Abstract

1 Disposition of oral brotizolam (0.5 mg) was studied in male patients with liver cirrhosis (patients) and in other patients (control) matched for age, weight, smoking and drinking habits. 2 Absorption of brotizolam was relatively rapid in both groups with a median peak time (range) of 1.0 (0.5-2.0) h. Peak concentrations were also similar with median values of 7.1 (3.2-10.7) ng/ ml in patients and 9.4 (2.9-19.0 ng/ml) in controls. 3 Elimination half-life was longer in patients than in controls. The median values were 12.8 (9.4-25) h and 6.9 (4.4-8.4) h respectively (P < 0.01). In two patients hardly any drug elimination was observed, indicating severe impairment of drug metabolizing activity. The prolongation of the elimination half-life was likely to be due to a decrease in clearance (45 ml/min in patients compared with 64 m/min in controls), and an increase in volume of distribution (0.62 1/kg and 0.39 1/kg respectively).4 Median values of protein unbound fraction of brotizolam were 9.2 (7.8-10.4) % in controls and 12.4 (10.4-18.9) % in patients. Clearance of unbound drug was 612 ml/min and 380 ml/min respectively.

Safe use of medication in patients with cirrhosis: pharmacokinetic and pharmacodynamic considerations

“…With regard to the receptor theory, at comparable (unbound) plasma levels of benzodiazepines, excessive sedation was noted in cirrhotics compared to controls [78][79][80]. Benzodiazepine levels in the CSF were not higher than those in controls [81].…”

Variables influencing patient satisfaction for hypnotics: difference between zolpidem and brotizolam

“…Our further interests were focused on the difference between satisfied and dissatisfied patients taking the same categorized agents as the short‐acting hypnotics, zolpidem and brotizolam, the most common hypnotics used for patients with insomnia in Japan. As it is known that the pharmacokinetics of zolpidem and brotizolam is affected by gender and age, that is, increased clearance in males taking zolpidem and younger subjects taking brotizolam, these factors may affect amount of sleep and patient satisfaction.…”

Pharmacokinetics of temazepam compared with other benzodiazepine hypnotics—some clinical consequences

“…In the elderly, brotizolam elimination half-life is twice as long as in the young due to decreased clearance (9). The elimination of brotizolam was also decreased in patients with liver cirrhosis (8). Age also affects the kinetics of loprazolam: elimination in the elderly was 20 hours as compared with 11 hours in the young It has been shown for triazolam, midazolam and brotizolam that no significant quantities of active metabolites are present in plasma, even during or after continuous administration (47,49,56).…”