Pharmacokinetics of intravenous ciprofloxacin in normal and renally impaired subjects

The pharmacokinetics of intravenous ciprofloxacin and its metabolites were characterized in 42 subjects with various degrees of renal function (group 1, CIcr (mL/min/1.73 m(2)) > 90, n = 10; group 2, CIcr 61-90, n = 11; group 3, CIcr 31-60, n = 11; group 4, CIcr less than or equal to 30, n = 10). The dosage regimens were-groups 1 and 2: 400 mg iv at 8 hourly intervals; group 3: 400 mg iv at 12 hourly intervals and group 4: 300 mg iv at 12 hourly intervals. Subjects received a single dose on days 1 and 5 and multiple doses on days 2-4. Multiple plasma and urine samples were collected on days 1 and 5 for the analysis of ciprofloxacin and its metabolites (M1, M2 and M3). Plasma concentrations (C-max and AUC) of ciprofloxacin and its M1 and M2 metabolites were significantly increased in subjects with reduced CIcr values (CIcr < 60 mL/min/1.73 m(2)) compared with normal subjects (CL(cr) > 90 mL/min/1.73 m(2)). A positive correlation was observed between ciprofloxacin clearance (CI) and CIcr with a slope of 0.29 (r(2) = 0.78) and between renal clearance (CIr) and CIcr with a slope of 0.19 (r(2) = 0.84). For patients with severe infections a dosage regimen of 400 mg iv 8 hourly is appropriate in patients with CIcr > 60 mL/min/1.73 m(2). In patients with CIcr values of 31-60 mL/min/1.73 m(2) a dosage regimen of 400 mg 12 hourly provides similar plasma concentrations to those observed for subjects with CIcr 61-90 mL/min/1.73 m(2) receiving 400 mg 8 hourly. Based on modeling of the plasma concentrations in subjects with CIcr less than or equal to 30 mL/min/1.73 m(2) a dosage regimen of 400 mg every 24 h will provide plasma concentrations similar to those observed in subjects with CIcr between 61-90 mL/min/1.73 m(2) given 400 mg every 8 h.