Single-Dose Pharmacokinetics of Ceftriaxone in Patients with End-Stage Renal Disease and Hemodialysis

Abstract

We report the pharmacokinetic parameters of ceftriaxone in 11 patients on hemodialysis with end-stage renal disease (ESRD; creatinine clearance < 5 ml/ min/1.73 m²). The patients were studied during the interdialysis period and during 4h of hemodialysis. The mean age was 53.4 years. After the administration of 1 g of ceftriazone during a constant intravenous infusion over a 30-min period, t_½ was 16.6 h, β was 0.0418 ± 0.0106 h^-1, V_D was 14.5 ± 3.0 liters/1.73 m² and Cl_p 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 μg/ml. This value dropped to 40.4 ± 4.7 μg/ml at the end of the 4th hour, indicating a significant 41% decay in blood levels during hemodialysis (p < 0.001). The t_½ decreased to 4.88 h, k_el rose to 0.142 ± 0.0250 h^-1 and Cl_p increased to 1.73 ± 0.44 liters/h. All values were highly significantly different (p < 0.001) from those during the interdialysis period. The plasma ceftriaxone concentration of 40.4 ± 4.7 μg/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_½ in patients with ESRD. Ceftriaxone is significantly dialyz-able, 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. If the interdialysis period is longer than 48 h an extra dose should be administered.

Clinical Pharmacokinetics of Ceftriaxone

“…However, a recent study reported a 41 % reduction in serum concentration (68 to 40 mg/L) and average tlh (16.6 to 4.88h) with 4-hour haemodialysis in II patients with end-stage renal disease (Garcia et al 1988). At 28 hours after a dose of ceftriaxone Ig including a 4-hour haemodialysis, plasma concentrations were still within the therapeutic range (40 mg/L).…”

“…Anephric patients with normal extrarenal clearance showed a moderate increase in tlh (14.4 to 17h) with greater V d (Garcia et al 1988;Wise et al 1985). Anephric patients with concurrent decrease in extrarenal clearance (> 80%), however, showed a significant prolongation of tlh (> 50h), requiring dose adjustment (Stoeckel et al 1984b).…”

Choreoathetosis Is a Possible Adverse Event of a Commonly Used Antibiotic

“…While its elimination half-life (T1/2) is 6–9 h in normal subjects, it prolongs to 16.6 h in patients with ESRD: creatinine clearance (CCr) ˂5 mL/min/1.73 m 2 [2]. Although CTX is dialyzable, its blood concentration achieves the bacteriocidal range during hemodialysis independent of CCr [2].…”

“…While its elimination half-life (T1/2) is 6–9 h in normal subjects, it prolongs to 16.6 h in patients with ESRD: creatinine clearance (CCr) ˂5 mL/min/1.73 m 2 [2]. Although CTX is dialyzable, its blood concentration achieves the bacteriocidal range during hemodialysis independent of CCr [2]. As it has a moderately longer T1/2 and is not affected by hemodialysis, the administration of a once-daily dose of CTX is rational and practical to eradicate susceptible organisms in patients with severely impaired renal function.…”

Considerations in Dosage Selection for Third Generation Cephalosporins

“…Abbreviations: HD = haemodialysis; PD = peritoneal dialysis; CAPD = continuous ambulatory peritoneal dialysis; NC = no change; qxh = every x hours. tion (14.4 to 17h) due to significant nonrenal elimination which may be facilitated by the increased free fraction often present in these patients (Garcia et al 1988;Wise & Wright 1985). Dosage adjustment in renal failure is not indicated for cefoperazone.…”