Summary
The advantages of continuous haemofiltration and haemodialysis over intermittent haemodialysis for the treatment of acute renal failure are well recognised. In intensive care patients, 4 different continuous procedures, arteriovenous and venovenous haemofiltration (CAVH and CVVH) or haemodialysis (CAVHD and CVVHD), are employed. These effective detoxification treatments require knowledge of their influence on drug disposition. Data on kinetics of drugs during continuous treatment are scarce and limited almost exclusively to the oldest and least effective procedure (CAVH). Selected dialysis membranes may adsorb drugs, as in the case of aminoglycosides. In addition, elimination of substances with large molecular weights may vary depending on the pore size of the membrane, as in the case of vancomycin. Thus, even if drug dosages can be based on pharmacokinetic studies, selection of a dialysis membrane not studied may cause unpredictable drug concentrations. With these limitations in mind and considering the available literature on pharmacokinetics in patients with renal failure, general guidelines for drug dosage during continuous renal replacement therapy can be given.
In haemofiltration, drug protein binding is the major factor determining sieving, i.e. the appearance of the drug in the ultrafiltrate. In haemodialysis, diffusion is added to ultrafiltration, and therefore the saturation of the combined dialysate and ultrafiltrate will decrease further with increasing dialysate flow rate. In continuous haemofiltration or haemodialysis the extracorporeal clearance can be calculated by multiplying the saturation value (estimated or, better, measured) with the ultrafiltrate and dialysate flow rate. Dividing the extracorporeal clearance by the total clearance (including the nonrenal clearance) gives the fraction of the dose removed due to extracorporeal elimination. Whether dosage recommendations available for anuric patients have to be modified or not can be decided on the basis of this value. In case of high nonrenal clearance, the degree of saturation is without clinical significance. Based on these considerations guidelines have been constructed for the effect of extracorporeal elimination on more than 120 different drugs commonly used in intensive care patients.
Similar content being viewed by others
References
Abshagen U, Betzien G, Endele R, Kaufmann B. Pharmacokinetics of intravenous and oral isosorbide-5-mononitrate. European Journal of Clinical Pharmacology 20: 269–275, 1981
Adair CG, Bridges JM, Desai ZR. Renal function in the elimination of oral melphalan in patients with multiple myeloma. Cancer Chemotherapy and Pharmacology 17: 185–188, 1986
Akintonwa A, Odutola TA, Edeki T, Mabadeje AFB. Hemodialysis clearance of chloroquine in uraemic patients. Therapeutic Drug Monitoring 8: 285–287, 1986
Aronoff GR, Sloan RS, Brier ME, Luft FC. The effect of piperacillin dose on elimination kinetics in renal impairment. European Journal of Clinical Pharmacology 24: 543–547, 1983
Bandai H, Tsubakihara Y, Yamato E, Yokoyama K, Okada N, et al. Pharmacokinetics of ofloxacin in severe chronic renal failure. Clinical Therapeutics 11: 210–218, 1989
Beermann B, Grind M. Clinical pharmacokinetics of some newer diuretics. Clinical Pharmacokinetics 13: 254–266, 1987
Benet LZ, Sheiner LB. Design and optimization of dosage regimens; pharmacokinetic data. In Goodman Gilman et al. (Eds) The pharmacological basis of therapeutics, 7th ed., pp. 1663–1733, Macmillan, New York, 1985
Bennett WM. Appendix: Practical guideline for drug dosing in renal failure. In Brenner et al. (Eds) Pharmacotherapy of renal disease and hypertension, pp. 349–400, Churchill Livingstone, New York, 1987
Bennett WM. Guide to drug dosage in renal failure. In Mammen et al. (Eds) Clinical pharmacokinetics drug data handbook 1989, pp. 39–90, ADIS Press, New Zealand, 1989
Bennett WM, Aronoff GR, Morrison G, Golper TA, Pulliam J, et al. Drug prescribing in renal failure: Dosing guidelines for adults. American Journal of Kidney Diseases 3: 155–193, 1983
Bircher J, Lotterer E (Eds). Klinisch-Pharmakologische Datensammlung, Gustav Fischer, Stuttgart, 1988
Bodenham A, Shelly MP, Park GR. The altered pharmacokinetics and pharmacodynamics of drugs commonly used in critically ill patients. Clinical Pharmacokinetics 14: 343–373, 1988
Boelaert J, Schurgers M, Matthys E, Daneels R, Van Peer A, et al. Itraconazole pharmacokinetics in patients with renal dysfunction. Antimicrobial Agents and Chemotherapy 32: 1595–1597, 1988
Böhler J, Reetze P, Keller E, Kramer A, Schollmeyer P. Rebound of vancomycin plasma levels after hemodialysis with highly permeable membranes. European Journal of Clinical Pharmacology, 42: 635–640, 1992
Bolton WK, Scheld WM, Spyker DA, Overby TL, Sande MA. Pharmacokinetics of moxalactam in subjects with various degrees of renal dysfunction. Antimicrobial Agents and Chemotherapy 18: 933–938, 1980
Bonati M, Traina GL, Villa G, Salvadeo A, Gentile MG, et al. Teicoplanin pharmacokinetics in patients with chronic renal failure. Clinical Pharmacokinetics 12: 292–301, 1987
Bortel L, Böhm R, Mooy J, Schiffers P, Rahn KH. Pharmacokinetics of nitrendipine in terminal renal failure. European Journal of Clinical Pharmacology 36: 467–471, 1989
Brazier JL, Pozet N, Faucon G, Traeger J, Hadj-Haissa A. Kinetics of a high dose of piretanide in renal failure. European Journal of Clinical Pharmacology 21: 307–310, 1982
Burgess ED, Duff HJ. Hemodialysis removal of propafenone. Pharmacotherapy 9: 331–333, 1989
Canaud B, Garred LJ, Christol J-P, Aubas S, Beraud JJ, et al. Pump assisted continuous venovenous hemofiltration for treating acute uremia. Kidney International 33 (Suppl. 24): 154–156, 1988
Carchman SH, Sica DA, Davis J, Crowe Jr JT, Wasserman AJ, et al. Steady-state plasma levels and pharmacokinetics of guanfacine in patients with renal insufficiency. Nephron 53: 18–23, 1989
Chauvin M, Sandouk P, Scherrmann JM, Farinotti R, Strumza P, et al. Morphine pharmacokinetics in renal failure. Anesthesiology 66: 327–331, 1987
Cigarran-Guldris S, Brier ME, Golper TA. Tobramycin clearance during simulated continuous arteriovenous hemodialysis. Contributions to Nephrology 93: 120–123, 1991
Colton CK, Henderson LW, Ford CA, Lysaght MJ. Kinetics of hemodiafiltration I. In vitro transport characteristics of a hollow fiber blood ultrafilter. Journal of Laboratory and Clinical Medicine 85: 355–371, 1975
Craig WA, Suh B. Changes in protein binding during disease. Scandinavian Journal of Infectious Disease (Suppl. 14): 239–244, 1978
Davies SP, Lacey F, Kox WJ, Brown EA. Pharmacokinetics of cefuroxime and ceftazidime in patients with acute renal failure treated by continuous arteriovenous haemodialysis. Nephrology Dialysis and Transplantation 6: 971–976, 1991
Duchin KL, Pierides AM, Heald A, Singhvi SM, Rommel AJ. Elimination kinetics of captopril in patients with renal failure. Kidney International 25: 942–947, 1984
Eykyn S, Phillips I, Evans J. Vancomycin for staphylococcal shunt site infections in patients on regular haemodialysis. British Medical Journal 3: 80–82, 1970
Faulds D, Heel C. Ganciclovir: a review of its antiviral activity, pharmacokinetic properties and therapeutic efficiency in cytomegalovirus infections. Drugs 39: 597–638, 1990
Fillastre J-P, Singlas E. Pharmacokinetics of newer drugs in patients with renal impairment: Part I. Clinical Pharmacokinetics 20: 293–310, 1991
Fillastre JP, Leroy A, Moulin B, Dhib M, Borsa-Lebas F, et al. Pharmacokinetics of quinolones in renal insufficiency. Journal of Antimicrobial Chemotherapy 26 (Suppl. B): 51–60, 1990
Gambertoglio JG. Appendix: drug reference tables. In Anderson et al. (Eds) Clinical use of drugs in patients with kidney and liver disease, pp. 312–333, Saunders, Philadelphia, 1981
Garzone PD, Kroboth PD. Pharmacokinetics of the newer benzodiazepines. Clinical Pharmacokinetics 16: 337–364, 1989
Geronemus R, Schneider N. Continuous arteriovenous hemodialysis: a new modality for treatment of acute renal failure. Transactions of the American Society of Artificial Internal Organs 30: 610–613, 1984
Gladziwa U, Klotz U, Krishna DR, Schmitt H, Glöckner WM, et al. Pharmacokinetics and dynamics of famotidine in patients with renal failure. British Journal of Clinical Pharmacology 26: 315–321, 1988
Golper TA, Saad A-MA, Morris CD. Gentamicin and phenytoin sieving through hollow-fiber polysulfone hemofilters. Kidney International 30: 937–943, 1986
Golper TA. Drug removal during continuous hemofiltration or hemodialysis. Contributions to Nephrology 93: 110–116, 1991
Grech-Belanger O, Langlois S, LeBoeuf E. Pharmacokinetics of diltiazem in patients undergoing continuous ambulatory peritoneal dialysis. Journal of Clinical Pharmacology 28: 477–480, 1988
Guay DRP, Awni WM, Findlay JWA, Halstenson CE, Abraham PA, et al. Pharmacokinetics and pharmacodynamics of codeine in end-stage renal disease. Clinical Pharmacology and Therapeutics 43: 63–71, 1988
Halstenson CE, Opsahl JA, Pence TV, Luke DR, Sirgo MA, et al. The disposition an dynamics of labetalol in patients on dialysis. Clinical Pharmacology and Therapeutics 40: 462–468, 1986
Hasegawa H, Itagaki N, Tsujino M, Takahashi K, Yamamoto Y, et al. Pharmacokinetics of cefmenoxime in renal-failure patients undergoing continuous arteriovenous hemofiltration. Japanese Journal of Antibiotics 41: 338–341, 1988
Hilt H, Keller F. Elimination von Pharmaka durch Hämofiltration. Grundlagen und Literaturdaten. Anästhesie, Intensivtherapie, Notfallmedizin 22: 278–282, 1987
Höffler D. Dosierung wichtiger Arzneimittel bei Niereninsuffizienz. Medizinische Welt 32: 875–879, 1981
Holdiness MR. Clinical pharmacokinetics of the antituberculosis drugs. Clinical Pharmacokinetics 9: 511–544, 1984
Holt DW, Storey GCA. Die Pharmacokinetik von Amiodaron. In Breithardt & Loogen (Eds) Neue Aspekte in der medikamentösen Behandlung von Tachyarrhythmien, pp. 75–78, Urban & Schwarzenberg, München, 1983
Janknegt R, Nube MJ, van den Hoogenband HM, Oldenhof HGJ, Steenhoek A, et al. Pharmacokinetics of methotrexate in continuous ambulatory peritoneal dialysis. Pharmaceutisch Week-blad Scientific Edition 10: 86–89, 1988
Kates RE, Leier CV. Dobutamine pharmacokinetics in severe heart failure. Clinical Pharmacology and Therapeutics 24: 537–541, 1978
Keller E. Peritoneal kinetics of different drugs. Clinical Nephrology 30 (Suppl. l): 24–28, 1988
Keller E. Drug therapy during continuous arteriovenous hemofiltration. In Hörl et al. (Eds) New perspectives in hemodialysis, peritoneal dialysis, arteriovenous hemofiltration, and plasmapheresis, pp. 117–127, Plenum Press, New York, 1989
Keller E, Fecht H, Böhler J, Schollmeyer P. Single dose kinetics of imipenem/cilastatin during continuous arteriovenous haemofiltration in intensive care patients. Nephrology Dialysis and Transplantation 4: 640–645, 1989
Keller E, Hoppe-Seyler G, Mumm R, Schollmeyer P. Influence of hepatic cirrhosis and end-stage renal disease on pharmacokinetics and pharmacodynamics of furosemide. European Journal of Clinical Pharmacology 20: 27–33, 1981
Keller E, Reetze P, Schollmeyer P. Drug therapy in patients undergoing continuous ambulatory peritoneal dialysis. Clinical pharmacokinetic considerations. Clinical Pharmacokinetics 18: 104–117, 1990
Keller F, Offermann G, Lode H. Supplementary dose after hemodialysis. Nephron 30: 220–227, 1982
Keller F, Schwarz A (Eds). Pharmacokinetik bei Niereninsuffizienz, Gustav Fischer, Stuttgart, 1987
Kiechel JR. Pharmacokinetics of guanfacine in patients with impaired renal function and in some elderly patients. American Journal of Cardiology 57: 18E–21E, 1986
Kirch W, Rose I, Demers HG, Leopold G, Pabst J, et al. Pharmacokinetics of bisoprolol during repeated oral administration to healthy volunteers and patients with kidney or liver disease. Clinical Pharmacokinetics 13: 110–117, 1978
Kleinbloesem CH, Brummelen P, Harten J, Danhof M, Breimer DD. Nifedipine: influence of renal function on pharmacokinetic/hemodynamic relationship. Clinical Pharmacology and Therapeutics 37: 563–574, 1985
Knauf H, Mutschler E. Pharmacodynamics and pharmacokinetics of xipamide in patients with normal and impaired kidney function. European Journal of Clinical Pharmacology 26: 513–520, 1984
Koup JR, Keller E, Neumann H, Stoeckel K. Ceftriaxone pharmacokinetics during peritoneal dialysis. European Journal of Clinical Pharmacology 30: 303–307, 1986
Kösters W, Klotschkoff P, Abshagen U. Pharmacokinetik von Isosorbid-5-Mononitrat bei Patienten mit fortgeschrittener Niereninsuffizienz. Medizinische Welt 14a: 2–4, 1981
Kraft D, Lode H. Elimination of ampicillin and gentamicin by hemofiltration. Klinische Wochenschrift 57: 195–196, 1979
Krakamp B, Tanswell P, Bozler G. Steady-state intravenous pharmacokinetics of pirenzepine in patients with differing degrees of renal dysfunction. European Journal of Clinical Pharmacology 36: 75–78, 1989
Kramer P, Wigger W, Rieger J, Matthaei D, Scheler F. Arteriovenous haemofiltration: a new and simple method for treatment of over-hydrated patients resistant to diuretics. Klinische Wochenschrift 55: 1121–1122, 1977
Kroh U, Hofmann W, Lennartz H. Pharmakokinetik und Dosisanpassung von Cefotaxim bei kontinuierlicher volumenkonstanter Hämofiltration (CVHF). Zeitschrift für antimikrobielle antineoplastische Chemotherapie 6: 99–105, 1988
Kronfol NO, Lau AH, Barakat MM. Aminoglycoside binding to polyacrylonitrile hemofilter membranes during continuous hemofiltration. Transactions of the American Society of Artificial Internal Organs 33: 300–303, 1987
Kronfol NO, Lau AH, Colon-Rivera J, Libertin CL. Effect of CAVH membrane types on drug-sieving coefficients and clearances. Transactions of the American Society of Artificial Internal Organs 32: 85–87, 1986
Krupp A, Leuwer M, Schmidt H, Eberhardt B. Die Pharmakokinetik von Azlocillin bei anurischen Patienten während der kontinuierlichen arteriovenösen Hämofiltration. Nieren- und Hochdruckkrankheiten 19: 524–529, 1990
Lee CC, Marbury TC. Drug therapy in patients undergoing haemodialysis. Clinical pharmacokinetic considerations. Clinical Pharmacokinetics 9: 42–66, 1984
Lehmann CR, Heironimus JD, Collins CB, O’Neil TJ, Pierson WP, et al. Metoclopramide kinetics in patients with impaired renal function and clearance by hemodialysis. Clinical Pharmacology and Therapeutics 37: 284–289, 1985
Levine JF. Vancomycin: a review. Medical Clinics of North America 71: 1135–1145, 1987
Levy G. Pharmacokinetics in renal disease. American Journal of Medicine 62: 461–465, 1977
Loos U, Musch E, Engel M, Hartlapp JH, Hügl E, et al. The pharmacokinetics of melphalan during intermittent therapy of multiple myeloma. European Journal of Clinical Pharmacology 35: 187–193, 1988
Lowenthal DT, Irvin JD, Merrill D, Saris S, Ulm E, et al. The effect of renal function on enalapril kinetics. Clinical Pharmacology and Therapeutics 38: 661–666, 1985
Maher JF. Influence of continuous ambulatory peritoneal dialysis on elimination of drugs. Peritoneal Dialysis Bulletin 7: 159–167, 1987
Manuel MA, Paton TW, Cornish WR. Drugs and peritoneal dialysis. Peritoneal Dialysis Bulletin 3: 117–125, 1983
Merdjan H, Baumelou A, Diquet B, Chick O, Singlas E. Pharmacokinetics of ornidazole in patients with renal insufficiency; influence of haemodialysis and peritoneal dialysis. British Journal of Clinical Pharmacology 19: 211–217, 1985
Morgan DJ, Ching MS, Raymond K, Bury RW, Mashford ML, et al. Elimination of amphothericin B in impaired renal function. Clinical Pharmacology and Therapeutics 34: 248–253, 1983
Morrison G, Chiang ST, Koepke HH, Walker BR. Effect of renal impairment and hemodialysis on lorazepam kinetics. Clinical Pharmacology and Therapeutics 35: 646–652, 1984
Naesdal J, Andersson T, Bodemar G, Larsson R, Regardh C-G, et al. Pharmacokinetics of [14C]omeprazole in patients with impaired renal function. Clinical Pharmacology and Therapeutics 40: 344–351, 1986
Ochs HR, Greenblatt DJ, Verburg-Ochs B. Ibuprofen kinetics in patients with renal insufficiency who are receiving maintenance hemodialysis. Arthritis and Rheumatism 28: 1430–1434, 1985
Olbricht C, Schurek HJ, Müller C. Die kontinuierliche spontane Hämofiltration (Kramer Technik). Ein neuer Weg in der Intensivtherapie des akuten Nierenversagens ohne aufwendige Dialysetechnik. Intensivmedizin 19: 275–279, 1982
Padrini R, Compostella L, Piovan D, Javarnaro A, Cucchini F, et al. Ajmaline test in a patient with chronic renal failure. A pharmacokinetic and pharmacodynamic study. Clinical Pharmacokinetics 21: 150–154, 1991
Paton TW, Cornish WR, Manuel MA, Hardy BG. Drug therapy in patients undergoing peritoneal dialysis. Clinical pharmacokinetic considerations. Clinical Pharmacokinetics 10: 404–426, 1985
Przechera M, Bengel D, Risler T. Pharmacokinetics of imipenem/cilastatin during continuous arteriovenous hemofiltration. Contributions to Nephrology 93: 131–134, 1991
Reetze-Bonorden P, Böhler J, Kohler C, Schollmeyer P, Keller E. Elimination of Vancomycin in patients on continuous arteriovenous hemodialysis. Contributions to Nephrology 93: 135–139, 1991
Reyad S, Barajas M, Swartz RD, Hyneck ML, Moustafa M. Drug removal during continuous arteriovenous hemofiltration. Contemporary Dialysis and Nephrology 5: 30–42, 1989
Reynolds JEF (Ed.). Martindale: the extra pharmacopoeia, 29th ed., Pharmaceutical Press, London, 1989
Roberts DE, Williams JD. Ciprofloxacin in renal failure. Journal of Antimicrobial Chemotherapy 23: 820–823, 1989
Rumpf KW, Rieger J, Ansorg R, Doht B, Scheler F. Binding of antibiotics by dialysis membranes and its clinical relevance. Proceedings of the European Dialysis and Transplant Association 14: 607–609, 1977
Schäfer GE, Döring C, Sodemann K, Russ A, Schröder HM. Continuous arteriovenous and venovenous hemodialysis in critically ill patients. Contributions to Nephrology 93: 23–28, 1991
Schunkert H, Kindler J, Gassmann M, Lahn W, Irmisch R, et al. Pharmacokinetics of ramipril in hypertensive patients with renal insufficiency. European Journal of Clinical Pharmacology 37: 249–256, 1989
Sear JW. Sufentanil disposition in patients undergoing renal transplantation: influence of choice of kinetic model. British Journal of Anaesthesiology 63: 60–67, 1989
Sica DA, Comstock T, Harford A, Eshelman F. Ranitidine pharmacokinetics in continuous ambulatory peritoneal dialysis. European Journal of Clinical Pharmacology 32: 587–591, 1987
Simon C, Stille W (Eds). Antibiotika-Therapie in Klinik und Praxis, 7th ed., Schattauer, Stuttgart, 1989
Singlas E, Fillastre J-P. Pharmacokinetics of newer drugs in patients with renal impairment: Part II. Clinical Pharmacokinetics 20: 389–410, 1991
Singlas E, Taburet AM, Landru I, Albin H, Ryckelinck JPh. Pharmacokinetics of ciprofloxacin tablets in renal failure; influence of haemodialysis. European Journal of Clinical Pharmacology 31: 589–593, 1987
Slugg PH, Haug MT, Bosworth C, Paganini EP. Comparitive vancomycin kinetics in intensive care unit patients with acute renal failure: intermittent hemodialysis versus continuous hemofiltration hemodialysis. Contributions to Nephrology 93: 140–142, 1991
Sommadossi J-P, Bevan R, Ling T, Lee F, Mastre B, et al. Clinical pharmacokinetics of ganciclovir in patients with normal and impaired renal function. Reviews of Infectious Diseases 10 (Suppl. 3): 507–514, 1988
Späth G (Ed.). Amiodaron, de Gruyter, Berlin, 1984
Sprenger KGB, Stephen H, Kratz W, Huber K, Franz HE. Optimizing of hemodiafiltration with modern membranes? Contributions to Nephrology 46: 43–60, 1985
Stevens PE, Davies SP, Brown EA, Riley B, Gower PE, et al. Continuous arteriovenous haemodialysis in critically ill patients. Lancet 2: 150–152, 1988
St. Peter WL, Redic-Kill KA, Halstenson CE. Clinical pharmacokinetics of antibiotics in patients with impaired renal function. Clinical Pharmacokinetics 22: 169–210, 1992
Thijssen HHW, Wolters J. The metabolic disposition of flucloxacillin in patients with impaired renal failure. European Journal of Clinical Pharmacology 22: 429–434, 1982
Toon S, Ross E, Gokal G, Rowland M. An assessment of the effects of impaired function and haemodialysis on the pharmacokinetics of fluconazole. British Journal of Clinical Pharmacology 29: 221–226, 1990
Vanholder R, Van Landschoot N, Smet DR, Schoots A, Ringoir S. Drug protein binding in chronic renal failure: evaluation of nine drugs. Kidney International 33: 996–1004, 1988
Vožeh S, Schmidlin O, Taeschner W. Pharmacokinetic drug data. Clinical Pharmacokinetics 13: 254–284, 1988
Weiss LG, Cars O, Danielson BG, Grahnen A, Wikström B. Pharmacokinetics of intravenous cefuroxime during intermittent and continuous arteriovenous hemofiltration. Clinical Nephrology 30: 282–286, 1988
Whelton A. Antibiotic pharmacokinetics and clinical application in renal insufficiency. Medical Clinics of North America 66: 267–281, 1982
Wiegers U, Hanrath P, Kuck KH, Pottage A, Graffner C, et al. Pharmacokinetics of tocainide in patients with renal dysfunction and during haemodialysis. European Journal of Clinical Pharmacology 24: 503–507, 1983
Williams AJ, McQuinn RL, Walls J. Pharmacokinetics of flecainide acetate in patients with severe renal impairment. Clinical Pharmacology and Therapeutics 43: 449–455, 1988
Wu MJ, Ing TS, Soung LS, Daugirdas JT, Hano JE, et al. Amantadine hydrochloride pharmacokinetics in patients with impaired renal function. Clinical Nephrology 17: 19–23, 1982
Zarowitz BJ, Anandan JV, Dumler F, Jayashankar J, Levin N. Continuous arteriovenous hemofiltration of aminoglycoside antibiotics in critically ill patients. Journal of Clinical Pharmacology 26: 686–689, 1986
Ziegler MG, Kennedy B, Morrissey E, O’Connor DT. Norepinephrine clearance, chromogranin A and dopamine β hydroxylase in renal failure. Kidney International 37: 1357–1362, 1990
Zini R, Riant P, Barre J, Tillement J-P. Disease-induced variations in plasma protein levels. Implications for drug dosage regimes: Part I. Clinical Pharmacokinetics 19: 147–159, 1990a
Zini R, Riant P, Barre J, Tillement J-P. Disease-induced variations in plasma protein levels. Implications for drug dosage regimes: Part II. Clinical Pharmacokinetics 19: 218–229, 1990b
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Reetze-Bonorden, P., Böhler, J. & Keller, E. Drug Dosage in Patients during Continuous Renal Replacement Therapy. Clin. Pharmacokinet. 24, 362–379 (1993). https://doi.org/10.2165/00003088-199324050-00002
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003088-199324050-00002