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Influence of mild liver impairment on the pharmacokinetics of tezosentan, a drug excreted unchanged into bile
Author(s) -
Dingemanse Jasper,
Van Giersbergen Paul L. M.
Publication year - 2004
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2003.01987.x
Subject(s) - pharmacokinetics , medicine , volume of distribution , urine , confidence interval , urology , distribution (mathematics) , population , pharmacology , mathematical analysis , mathematics , environmental health
Aims To investigate the effect of mild liver impairment on the pharmacokinetics of tezosentan. Methods Eleven patients with mild liver impairment and eight healthy subjects received an intravenous infusion of 50 mg h −1 tezosentan for 1 h. Plasma and urine concentrations were determined during and following termination of the infusion. Results The pharmacokinetic parameters presented as geometric means [95% confidence interval (CI)] for clearance, volume of distribution and terminal half‐life were 30 (22, 40) and 42 (36, 48) l h −1 , 28 (19, 42) and 19 (16, 23) l, and 4.5 (2.9, 7.0) and 3.6 (2.9, 4.5) h in liver patients and healthy subjects, respectively. The ratios (liver patients/healthy subjects) of these geometric means (95% CI) were 0.71 (0.47, 1.1), 1.5 (0.87, 2.6), and 1.3 (0.69, 2.3), respectively. A two‐compartment model accurately fitted the concentration–time data. In both groups approximately 4% of the dose was excreted unchanged into urine. Conclusions Although there was a slight trend towards a decreased clearance, the pharmacokinetics of tezosentan in patients with mild liver impairment were similar to those in healthy subjects. Therefore, no dose adaptation seems to be needed in this patient population.