caa a22 4500 477057233 CHVBK 20180405111349.0 cr unu---uuuuu 170330e19960601xx s 000 0 eng 10.1007/s002280050112 doi (NATIONALLICENCE)springer-10.1007/s002280050112 Comparison of the pharmacokinetics of tirilazad mesylate in healthy volunteers and stable subjects with mild liver cirrhosis [Elektronische Daten] [L. K. Pearson, J. C. Fleishaker, G. R. Peters] Objective: The pharmacokinetics of tirilazad mesylate and an active reduced metabolite, U89678, were studied in 7 volunteers with mild cirrhosis of the liver and seven age, sex, weight and smoking status matched healthy normal volunteers. Subjects received a single intravenous infusion of 2.0 mg ⋅kg−1 tirilazad mesylate over 10 min. Results: Mean tirilazad AUC0-∞ was 8.83 μmol h⋅l−1 and 18.6 μmol h⋅l−1 in healthy volunteers and cirrhotic subjects, respectively. Mean tirilazad clearance in cirrhotics (12.7 l⋅h−1) was approximately 2.1 fold lower than in healthy volunteers (27.8 l⋅h−1). The differences were statistically significant. Mean U-89678 AUC0-∞ in cirrhotic subjects (3.88 μmol h⋅l−1) was 2.5 fold higher than in healthy controls (1.53 μmol h⋅l−1), but the difference was marginally significant. Conclusion: These results indicate that clearance of both tirilazad mesylate and U89678 is decreased in subjects with hepatic impairment. This observation may be attributed either to decreases in liver blood flow and/or intrinsic clearance. The results of this study thus suggest that increased monitoring and or a reduction in tirilazad dosing may be necessary in patients with hepatic impairment. Springer-Verlag Berlin Heidelberg, 1996 Key words Tirilazad mesylate nationallicence Cirrhosis nationallicence human nationallicence hepatic clearance nationallicence U89678 nationallicence active metabolite nationallicence Pearson L. K. Clinical Pharmacokinetics Unit, 7215-24-2, The Upjohn Company, Kalamazoo, MI, 49007, USA, US aut Fleishaker J. C. Clinical Pharmacokinetics Unit, 7215-24-2, The Upjohn Company, Kalamazoo, MI, 49007, USA, US aut Peters G. R. Clinical Research Unit, The Upjohn Company, Kalamazoo, MI, USA, US aut https://doi.org/10.1007/s002280050112 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050112 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pearson L. K. Clinical Pharmacokinetics Unit, 7215-24-2, The Upjohn Company, Kalamazoo, MI, 49007, USA, US aut NATIONALLICENCE 700 1- Fleishaker J. C. Clinical Pharmacokinetics Unit, 7215-24-2, The Upjohn Company, Kalamazoo, MI, 49007, USA, US aut NATIONALLICENCE 700 1- Peters G. R. Clinical Research Unit, The Upjohn Company, Kalamazoo, MI, USA, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer