Subscribe to RSS
DOI: 10.1055/s-2005-872509
© Georg Thieme Verlag Stuttgart · New York
Antimikrobielle Therapie bei Kindern und Jugendlichen mit Nieren- und Leberinsuffizienz
Antimicrobial Agents in Pediatric Cancer Patients with Hepatic or Renal ImpairmentPublication History
Publication Date:
15 November 2005 (online)
![](https://www.thieme-connect.de/media/klinpaed/2005S1/lookinside/thumbnails/10.1055-s-2005-872509-1.jpg)
Zusammenfassung
In der Supportivtherapie von Kindern und Jugendlichen mit bösartigen Erkrankungen oder nach Blutstammzelltransplantation sind antimikrobielle Substanzen eine der am häufigsten eingesetzten Arzneimittel. Die meisten dieser Substanzen werden unverändert über die Nieren und/oder nach Metabolisierung über die Leber aus dem Körper eliminiert. Funktionsstörungen von Nieren und Leber haben z. T. ausgeprägte Effekte auf die Pharmakologie antimikrobieller Substanzen mit der Konsequenz einer Dosismodifikation, um unerwünschte Arzneimittelwirkungen vor allem durch Akkumulation der Muttersubstanz und/oder ihrer Metabolite zu verhindern. Voraussetzung zur Vermeidung derartig hervorgerufener Arzneimittelwirkungen ist die genaue Kenntnis häufig eingesetzter Substanzen und eine sorgfältige Abwägung von Nutzen und Risiken antimikrobieller Interventionen. Der vorliegende Beitrag enthält eine Übersicht über die Mechanismen der Clearance von Arzneimitteln bei normaler und eingeschränkter Nieren- und Leberfunktion, die Implikationen für die antimikrobielle Therapie und Dosierungsempfehlungen für pädiatrische Patienten mit bösartigen Erkrankungen und eingeschränkter Nieren- bzw. Leberfunktion.
Abstract
Antimicrobial agents are among the most frequently prescribed therapeutics in the supportive care of children and adolescents with cancer or following hematopoietic stem cell transplantation. Most of these agents are cleared from the body by elimination of unchanged drug by the kindney and/or metabolism by the liver. Impaired renal and hepatic function may have profound effects on the pharmacokinetics and pharmacodynamics of antimicrobial agents, necessitating modification of the dosage regimen in order to avoid toxicity through accumulation of the parent and/or its metabolites. Key to minimize such toxicities is a thorough understanding of the antimicrobial drug armamentarium and a careful evaluation of benefits and risks of antimicrobial interventions. This article reviews the mechanisms of renal and hepatic drug clearance in the normal state and in the state of functional impairment, their implications for antimicrobial therapy and dosage recommendations for pediatric cancer patients with impaired renal or hepatic function.
Schlüsselwörter
antimikrobielle Substanzen - Niereninsuffizienz - Leberinsuffizienz - Kinder - Krebs
Key words
antimicrobial agents - hepatic impairment - renal impairment - children - cancer
Literatur
- 1 AHFS Drug Information. www.ashp.org/ahfs
- 2 Arzneimittelinformation für Ärzte und Apotheker. www.fachinfo.de
- 3 Atkinson A J, Susla G M. Pharmacokinetics in patients requiring renal replacement therapy. In: Atkinson AJ, Daniels CE, Dedrick RL, Grudzinskas CV, Markey SP. Principles of clinical pharmacology. Academic Press, San Diego 2001; 51-62
- 4 Atkinson A J. Effects of renal disease on pharmacokinetics. In: Atkinson AJ, Daniels CE, Dedrick RL, Grudzinskas CV, Markey SP. Principles of clinical pharmacology. Academic Press, San Diego 2001; 43-49
- 5 Bergquist C, Lindegard J, Salmonson T. Dosing recommendations in liver disease. Clin Pharmacol Ther. 1999; 66 201-204
- 6 Blaschke T F. Protein binding and kinetics of drugs in liver diseases. Clin Pharmacokinet. 1977; 2 32-44
- 7 CDER, CBER .Pharmacokinetics in patients with impaired hepatic function: study design, data analysis, and impact on dosing and labeling. Guidance for Industry. Rockville, FDA 2003. http://www.fda.gov/cder/guidance/3625fnl.doc
- 8 Cockcroft D W, Gault M H. Prediction of creatinine clearance from serum creatinine. Nephron. 1976; 16 31-41
- 9 Cooper B E, Nester T J, Armstrong D K, Dasta J F. High serum concentrations of mezlocillin in a critically ill patient with renal and hepatic dysfunction. Clin Pharm. 1986; 5 764-766
- 10 Craig R M, Murphy P, Gibson T P, Quintanilla A, Chao G C, Cochrane C, Patterson A, Atkinson A J. Kinetic analysis of D-xylose absorption in normal subjects and in patients with chronic renal failure. J Lab Clin Med. 1983; 101 496-506
- 11 Dettli L. Individualization of drug dosage in patients with renal disease. Med Clin North Am. 1974; 58 977-985
- 12 Evans R S, Pestotnik S L, Classen D C, Clemmer T P, Weaver L K, Orme J F, Lloyd J F, Burke J P. A computer-assisted management program for antibiotics and other antiinfective agents. N Engl J Med. 1998; 338 232-238
- 13 Gaspari F, Perico N, Remuzzi G. Measurement of glomerular filtration rate. Kidney Int. 1997; 63 (Suppl) S151-S154
- 14 George J, Murray M, Byth K, Farrell G C. Differential alterations of cytochrome P450 proteins in livers from patients with severe chronic liver disease. Hepatology. 1995; 21 120-128
- 15 Green L, Dick J D, Goldberger S P, Angelopulos C M. Prolonged elimination of piperacillin in a patient with renal and liver failure. Drug Intell Clin Pharm. 1985; 19 427-429
- 16 Kuemmerle H P, Murakawa T. (eds) .Pharmacokinetics of antimicrobial agents. Principles - methods - application. Taylor & Francis Inc., Abingdon, UK 1992
- 17 Lebel M H. Pharmacology of antimicrobial agents in children with hepatic dysfunction. Pediatr Infect Dis. 1986; 5 686-690
- 18 Lee W M. Drug-induced hepatotoxicity. N Engl J Med. 1995; 333 1118-1127
- 19 Livornese L L, Benz R L, Ingerman M J, Santoro J. Antibacterial agents in renal failure. Infect Dis Clin North Am. 1995; 9 591-614
- 20 Maderazo E G. Antibiotic dosing in renal failure. Med Clin North Am. 1995; 79 919-933
- 21 Möller E, McIntosh J F, Slyke D D Van. Studies of urea excretion. II. Relationship between urine volume and the rate of urea excretion in normal adults. J Clin Invest. 1929; 6 427-465
- 22 Nightingale P G, Adu D, Richards N T, Peters M. Implementation of rules based computerised bedside prescribing and administration: intervention study. BMJ. 2000; 320 750-753
- 23 Papadakis M A, Arieff A I. Unpredictability of clinical evaluation of renal function in cirrhosis. Prospective study. Am J Med. 1987; 82 945-952
- 24 Pugh R N, Murray-Lyon I M, Dawson J L, Pietroni M C, Williams R. Transsection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973; 60 646-649
- 25 Rahn K H, Heidenreich S, Bruckner D. How to assess glomerular function and damage in humans. J Hypertens. 1999; 17 309-317
- 26 Reidenberg M M, Drayer D E. Alteration of drug-protein binding in renal disease. Clin Pharmacokinet. 1984; 9 (Suppl 1) 18-26
- 27 Reidenberg M M. Renal function and drug action. WB Saunders, Philadelphia 1971
- 28 Reidenberg M M. The biotransformation of drugs in renal failure. Am J Med. 1977; 62 482-485
- 29 Rind D M, Safran C, Phillips R S, Wang Q, Calkins D R, Delbanco T L, Bleich H L, Slack W V. Effect of computer-based alerts on the treatment and outcomes of hospitalized patients. Arch Intern Med. 1994; 154 1511-1517
- 30 Rodighiero V. Effects of liver disease on pharmacokinetics. An update. Clin Pharmacokinet. 1999; 37 399-431
- 31 Rollins D E, Klaassen C D. Biliary excretion of drugs in man. Clin Pharmacokinet. 1979; 4 368-379
- 32 Rowland M, Benet L Z, Graham G G. Clearance concepts in pharmacokinetics. J Pharmacokinet Biopharm. 1973; 1 123-136
- 33 Schwartz G J, Haycock G B, Edelmann C M, Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics. 1976; 58 259-263
- 34 Susla G M, Atkinson A J. Effects of liver disease on pharmacokinetics. In: Atkinson AJ, Daniels CE, Dedrick RL, Grudzinskas CV, Markey SP. Principles of clinical pharmacology. Academic Press, San Diego 2001; 63-74
- 35 Thomson Micromedex. www.micromedex.com/
- 36 Toto R D. Conventional measurement of renal function utilizing serum creatinine, creatinine clearance, inulin and para-aminohippuric acid clearance. Curr Opin Nephrol Hypertens. 1995; 4 505-509
- 37 Tschida S J, Vance-Bryan K, Zaske D E. Anti-infective agents and hepatic disease. Med Clin North Am. 1995; 79 895-917
- 38 Westphal J F, Vetter D, Brogard J M. Hepatic side-effects of antibiotics. J Antimicrob Chemother. 1994; 33 387-401
- 39 Wilkinson G R, Shand D G. Commentary: a physiological approach to hepatic drug clearance. Clin Pharmacol Ther. 1975; 18 377-390
Priv.Doz. Dr. med. Andreas H. Groll
Klinik und Poliklinik für Kinder- und Jugendmedizin · Pädiatrische Hämatologie/Onkologie · Universitätsklinikum Münster
Albert Schweitzer Straße 33
48129 Münster
Phone: +49/2 51/8 34 77 42
Fax: +49/2 51/8 34 78 28
Email: grollan@ukmuenster.de