Single-dose pharmacokinetics of ceftriaxone in patients with end-stage renal disease and hemodialysis.

We report the pharmacokinetic parameters of ceftriaxone in 11 patients on hemodialysis with end-stage renal disease (ESRD; creatinine clearance less than 5 ml/min/1.73 m2). The patients were studied during the interdialysis period and during 4 h of hemodialysis. The mean age was 53.4 years. After the administration of 1 g of ceftriaxone during a constant intravenous infusion over a 30-min period, t 1/2 was 16.6 h, beta was 0.0418 +/- 0.0106 h-1, VD was 14.5 +/- 3.0 liters/1.73 m2 and Clp was 0.40 +/- 0.05 liters/h for the interdialysis period. Hemodialysis started 24 h after the infusion. The initial plasma ceftriaxone concentration was 68.6 +/- 10.8 micrograms/ml. This value dropped to 40.4 +/- 4.7 micrograms/ml at the end of the 4th hour, indicating a significant 41% decay in blood levels during hemodialysis (p less than 0.001). The t 1/2 decreased to 4.88 h, kel rose to 0.142 +/- 0.0250 h-1 and Clp increased to 1.73 +/- 0.44 liters/h. All values were highly significantly different (p less than 0.001) from those during the interdialysis period. The plasma ceftriaxone concentration of 40.4 +/- 4.7 micrograms/ml at the end of hemodialysis was well within the therapeutic range of the drug. We conclude that ceftriaxone has a moderated increase in t 1/2 in patients with ESRD. Ceftriaxone is significantly dialyzable, however, the plasma concentrations are in the therapeutic range by the end of a 4-hour hemodialysis, 28 h after the administration of the drug. We propose that 1 g given intravenously before each hemodialysis will be sufficient to keep the patient's plasma concentrations within the therapeutic range until the next hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)