PHARMACOKINETICS OF CEFODIZIME IN VOLUNTEERS WITH NORMAL OR IMPAIRED RENAL-FUNCTION

The pharmacokinetics of single, 1- or 2-g intravenous doses of cefodizime were studied in subjects with normal, impaired renal function or requiring chronic hemodialysis. Drug concentrations were measured using high-performance liquid chromatography. Forty-five subjects (20 with creatinine clearance of greater than or equal to 90 mL/min, 15 with creatine clearances between 5 and 89 mL/min, and 10 requiring chronic hemodialysis) were studied. The concentration-time curve of cefodizime was best represented by an open two-compartment model. The elimination half-lives in subjects with normal (Group 1) and impaired renal function (Group 2) or requiring chronic hemodialysis (Group 3) were 4.14 +/- 1.55, 5.10 +/- 2.24, and 10.1 +/- 6.01 hours, respectively (Group 3 versus 1 or 2, P < .05; Group 1 versus 2, P > .05). The total body (serum) clearances in the same groups were 3 +/- 0.52, 2.22 +/- 0.61, and 0.99 +/- 0.33 L/hour, respectively (Group 1 versus 2 or 3, P < .05; Group 2 versus 3, P < .05). Although renal function has an effect on the pharmacokinetics of cefodizime, its effect on the elimination half life is marginal in subjects with creatinine clearance of more than 25 mL/min. In individuals with more severe renal impairment or those requiring chronic hemodialysis, dosage adjustment would be required.