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 functi on (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 equa l to 30, n = 10). The dosage regimens were-groups 1 and 2: 400 mg iv a t 8 hourly intervals; group 3: 400 mg iv at 12 hourly intervals and gr oup 4: 300 mg iv at 12 hourly intervals. Subjects received a single do se 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 cipr ofloxacin and its metabolites (M1, M2 and M3). Plasma concentrations ( C-max and AUC) of ciprofloxacin and its M1 and M2 metabolites were sig nificantly increased in subjects with reduced CIcr values (CIcr < 60 m L/min/1.73 m(2)) compared with normal subjects (CL(cr) > 90 mL/min/1.7 3 m(2)). A positive correlation was observed between ciprofloxacin cle arance (CI) and CIcr with a slope of 0.29 (r(2) = 0.78) and between re nal clearance (CIr) and CIcr with a slope of 0.19 (r(2) = 0.84). For p atients 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 patient s with CIcr values of 31-60 mL/min/1.73 m(2) a dosage regimen of 400 m g 12 hourly provides similar plasma concentrations to those observed f or 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 observe d in subjects with CIcr between 61-90 mL/min/1.73 m(2) given 400 mg ev ery 8 h.