Steady-state levels of pefloxacin and its metabolites in patients with severe renal impairment

Summary Twenty patients (aged 26–70 years) with severely impaired renal function received pefloxacin twice daily for 5 days as 12 mg·kg^–1 administered as a 1 h i.v. infusion, or 800 mg administered as tablets.On Day 5 the minimal and maximal plasma concentrations were 5.9 and 11.5 mg·l^–1 respectively, after the infusion, and 8.0 and 10.4 mg·l^–1, respectively, after oral administration. The steady-state level of the N-desmethyl metabolite ranged from 0.9 (infusion) to 1.2 mg·l^–1 (oral route), and that of the N-oxide metabolite ranged from 6.2 (infusion) to 9.0 mg·l^–1 (oral route). The minimal concentration of unchanged drug was related to the age of the patients (infusion), but the N-oxide concentration was influenced by the degree of renal impairment (both routes).The pefloxacin levels were similar to those achieved in healthy subjects, but reduced renal function leads accumulation of its biotransformation products, especially of the N-oxide metabolite which lacks antibacterial activity.