| Abstrakt: |
Objective: This open-label, parallel-group study determined the pharmacokinetics of garenoxacin in subjects with severe renal impairment, including subjects maintained on dialysis.Research design and methods: Subjects were assigned to one of four groups according to their underlying renal function: creatinine clearance (CLcr) > 80 mL/min, CLcr < 30 mL/min, hemodialysis (HD), and continuous ambulatory peritoneal dialysis (CAPD). Subjects received a single oral 600-mg dose of garenoxacin. Administration of garenoxacin to subjects receiving hemodialysis was completed in two phases separated by 14 days: 3 h before HD (phase 1) and immediately after HD (phase 2).Main outcome measures: Plasma and urine or dialysate samples were analyzed for garenoxacin, and single-dose pharmacokinetic parameters were estimated. Safety was assessed.Results: Twenty-five subjects received garenoxacin. Compared with healthy controls, garenoxacin area under the concentration–time curve (AUC) and maximum plasma concentration were increased by 51% and lowered by 20%, respectively, in subjects with severe renal impairment. The terminal half-life was prolonged in subjects with severe renal impairment compared with healthy controls (26.5 ± 7 h vs 14.4 ± 3 h, respectively). In subjects receiving HD or CAPD, removal of garenoxacin from systemic circulation was relatively inefficient (HD, 1.5–11.5%; CAPD, 3%), suggesting no need for a supplemental dose of garenoxacin after dialysis. Garenoxacin was well tolerated.Conclusions: Based on the broad therapeutic index of garenoxacin, the effects of renal impairment on garenoxacin exposure are not considered clinically significant. There was a modest increase in AUC in subjects with severe renal impairment and the magnitude of the changes was not considered clinically relevant. [ABSTRACT FROM AUTHOR] |
