title: No influence of moderate hepatic impairment on the pharmacokinetics of lumiracoxib, an oral COX-2 selective inhibitor.
abstract: The aim of this study was to evaluate the influence of hepatic impairment on the pharmacokinetics (PK) of the novel cyclooxygenase-2 (COX-2) selective inhibitor lumiracoxib (Prexige), so that dose recommendations for clinical use can be provided. This was an open-label, single dose, case-controlled study in which eight subjects with liver cirrhosis classed as moderate hepatic impairment (Child-Pugh score: 7-9) and eight demographically-matched healthy subjects received a single oral 400 mg dose of lumiracoxib. Routine safety assessments were made and blood samples were taken for determination of lumiracoxib concentrations for 96 h post dose. The ex vivo binding of lumiracoxib to plasma proteins was determined pre dose and at 2 and 12 h post dose. An analysis of variance was used to detect differences in PK parameters (AUC, Cmax and Tmax) between the treatment groups. There were no significant differences between subjects with moderate hepatic insufficiency and healthy subjects in the area under the lumiracoxib plasma concentration-time curves (AUC(0-infinity)): 29.2 +/- 6.7 microg h ml(-1) versus 28.7 +/- 6.3 mircrog h ml(-1). The rate of absorption of lumiracoxib was not significantly altered by hepatic impairment based on Cmax and Tmax. The protein-bound fraction of lumiracoxib exceeded 98% both in healthy control subjects and in those with moderate hepatic insufficiency. A single dose of 400 mg lumiracoxib was well tolerated. In conclusion, no dose adjustments appear to be required when lumiracoxib is administered to patients with either mild or moderate hepatic impairment.
authors.affiliation: Departments of Exploratory Clinical Development, Biostatistics, and Bioanalytics, Novartis Pharmaceuticals, East Hanover, NJ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kalbag
authors.forename: C-M
authors.initials: CM
authors.lastname: Yeh
authors.forename: S
authors.initials: S
authors.lastname: Milosavljev
authors.forename: K
authors.initials: K
authors.lastname: Lasseter
authors.forename: S
authors.initials: S
authors.lastname: Oberstein
authors.forename: C
authors.initials: C
authors.lastname: Rordorf
mesh_terms: D000284:Administration, Oral; D019540:Area Under Curve; D001663:Bilirubin / Q000097:blood / Q000737:chemistry; D016022:Case-Control Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004008:Diclofenac / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D008107:Liver Diseases / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009930:Organic Chemicals / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011517:Prothrombin Time / Q000379:methods; D012709:Serum Albumin / Q000737:chemistry; D013557:Switzerland; D013607:Tablets; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016861:Cyclooxygenase Inhibitors; D009930:Organic Chemicals; D012709:Serum Albumin; D013607:Tablets; D004008:Diclofenac; D001663:Bilirubin; C473384:lumiracoxib