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)
Losno Garcia
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R
Department of Medicine, San Marcos University, Lima, Peru.
Santivañez
V
V
Battilana
C A
CA
D000328:Adult; D000368:Aged; D001424:Bacterial Infections / Q000517:prevention & control; D001798:Blood Proteins / Q000378:metabolism; D002443:Ceftriaxone / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D006435:Renal Dialysis
D001798:Blood Proteins; D002443:Ceftriaxone