Abstract
Serum concentrations of ceftriaxone (RocephinTM), a third generation cephalosporin, were monitored in 5 operative intensive care patients suffering from acute renal failure (ARF) and compared to those of 7 patients without renal disturbance. For a period of 7 days, a fixed dose of 2 g/day was given by a 15 min infusion. Pharmacokinetic parameters were calculated by fitting all serum and urine data measured over the period of treatment. Ceftriaxone free fraction was measured on days 2 and 7. There was no evidence for an intraindividual change in ceftriaxone-clearance during the observation period. Ceftriaxone renal clearance was closely dependent on creatinine clearance according to a linear regression expressed by Clren=0.14 Clcrea+2.2 (r=0.951,p<0.0001). Total clearance was also associated with creatinine clearance: Cltot=0.19 Clcrea+8.2 (r=0.964,p<0.0001). Related to the free fraction, renal clearance was in the range of the glomerular filtration rate. Non-renal clearance was strongly decreased when related to the free fraction indicating that biliary excretion is also impaired in patients with acute renal failure. Obviously no compensatory increase in hepatic ceftriaxone clearance takes place. It is concluded that elimination of ceftriaxone may be strongly impaired during acute renal failure in surgical intensive care patients and that dosage should be restricted according to degree of the impairment of creatinine clearance.
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References
Arvidsson A, Alvan G, Angelin B, Borga O, Nord CE (1982) Ceftriaxone: renal and biliary excretion and effect on the colon microflora. J Antimicrob Chemother 10:207–215
Neu HC, Meropol NJ, Fu KP (1981) Antibacterial activity of ceftriaxone (Ro 13-9904) a β-lactamase-stable cephalosporin. Antimicrob Agents Chemother 19:414–423
Campos AR, Herraez FXV, Marcos RJ, Amer JG, Porcar RC, Lucia PI (1980) Drug use in an intensive care unit and its relation to survival. Intensive Care Med 6:163–168
Cohen D, Appel G, Scully B, Neu HC (1983) Pharmacokinetics of ceftriaxone in patients with renal failure and in those undergoing hemodialysis. Antimicrob Agents Chemother 24:529–532
McNamara PJ, Gibaldi M, Stoeckel K (1983) Volume of distribution terms for a drug (ceftriaxone) exhibiting concentration-dependent protein binding I. Theoretical considerations. Eur J Clin Pharmacol 25:399–405
Angehrn P, Probst PJ, Reiner R, Then RL (1980) Ro 13-9904, a long-acting broad-spectrum cefalosporin. Antimicrob Agents Chemother 18:913–921
Patel IH, Chen S, Parsonnet M, Hackman MR, Brooks MA, Konikoff J, Kaplan SA (1981) Pharmacokinetics of ceftriaxone in humans. Antimicrob Agents Chemother 20:634–641
Stoeckel K, McNamara PJ, Hoppe-Seyler G, Blumberg A, Keller E (1983) Single-dose ceftriaxone kinetics in functionally anephric patients. Clin Pharmacol Ther 33:633–641
Hary L, Andrejak M, Leleu S, Orfila J, Capron JP (1989) The pharmacokinetics of ceftriaxone and cefotaxime in cirrhotic patients with ascites. Eur J Clin Pharmacol 36:613–616
Stoeckel K, Tuerk H, Trueb V, McNamara PJ (1984) Single-dose ceftriaxone kinetics in liver insufficiency. Clin Pharmacol Ther 36:500–509
Hayton WL, Schandlik R, Stoeckel K (1986) Biliary excretion and pharmacokinetics of ceftriaxone after cholecystectomy. Eur J Clin Pharmacol 30:445–451
Krahman S, Khan F, Patel S, Seriff N (1979) Renal failure in the intensive care unit. Crit Care Med 7:263–266
Schuster HP (1980) Akutes Nierenversagen nach großen Operationen. Dtsch Med Wochenschr 107:1633–1634
Trautmann KH, Haefelfinger P (1981) Determination of the cephalosporin Ro 13-9904 in plasma, urine, and bile by means of ion-pair reversed phase chromatography J High Res Chromatogr 4:54–59
Dixon WJ (1987) BMDP biomedical computer programs, University of California Press, Berkeley, Calif
Weber W (1988) Zur Pharmakokinetik des Thiamins im Plasma und im Urin: Berechnung einer nicht-linearen Eliminationskinetik. Thesis, Free University, Berlin
Rescigno A, Segre G (1966) Drug and tracer kinetics. Blaisdell, Waltham, Mass. p 86
Veng-Pederson P (1988) Linear and non-linear system approaches in pharmacokinetics: How much do they have to offer? I. General considerations. J Pharmacokinet Biopharm 16:413–471
Heinemeyer G, Roots I, Gramm H-J, Dennhardt R (1985) Induction and inhibition of drug elimination in critical care patients as shown by pentobarbital and metamizol clearance. Biochem Pharmacol 34:413–414
Heinemeyer G, Gramm H-J, Meschede V, Link J, Dennhardt R, Roots I (1988) Hepatische Arzneimittelclearance bei operativen Intensivpatienten mit akutem Nierenversagen. Z Gastroenterol 26:32
Heinemeyer G, Roots I, Lestau P, Klaiber H-R, Dennhardt R (1986) D-glucaric acid excretion in critical care patients—comparison to 6β-hydroxycortisol excretion and serum y-glutamyltranspeptidase activity and relation to multiple drug therapy. Br J Clin Pharmacol 21:9–18
Balant L, Dayer P, Auckentaler R (1985) Clinical pharmacokinetics of the third generation cephalosporins. Clin Pharmacokinet 10:101–143
Stoeckel K (1983) Pharmacokinetics of ceftriaxone, a long acting broad-spectrum cephalosporin. In: Progress in therapy of bacterial infections. A new cephalosporin ceftriaxone. Excerpta Medica, Amsterdam, pp 5–20
Ti TY, Lee HS, Lee EJC (1989) Pharmacokinetics of ceftriaxone in patients with renal failure on hemofiltration. Eur J Clin Pharmacol 36:[Suppl] A130
Joos B, Luethy R, Muehlen E, Siegenthaler W (1984) Variability of ceftriaxone pharmacokinetics in hospitalized patients with severe infections. Am J Med 77 (4C):59–62
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Heinemeyer, G., Link, J., Weber, W. et al. Clearance of ceftriaxone in critical care patients with acute renal failure. Intensive Care Med 16, 448–453 (1990). https://doi.org/10.1007/BF01711224
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DOI: https://doi.org/10.1007/BF01711224