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  • Title: Pharmacokinetics of oral brotizolam in patients with liver cirrhosis.
    Author: Jochemsen R, Joeres RP, Wesselman JG, Richter E, Breimer DD.
    Journal: Br J Clin Pharmacol; 1983; 16 Suppl 2(Suppl 2):315S-322S. PubMed ID: 6661377.
    Abstract:
    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. 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. 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 less than 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 ml/min in controls), and an increase in volume of distribution (0.62 l/kg and 0.39 l/kg respectively). 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.
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