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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. Jul 6, 2015; 4(3): 330-344
Published online Jul 6, 2015. doi: 10.5527/wjn.v4.i3.330
Pharmacokinetic and pharmacodynamic considerations of antimicrobial drug therapy in cancer patients with kidney dysfunction
Frieder Keller, Bernd Schröppel, Ulla Ludwig
Frieder Keller, Bernd Schröppel, Ulla Ludwig, Section of Nephrology, Department of Internal Medicine 1, University Hospital, D-89070 Ulm, Germany
Author contributions: Keller F contributed to the pharmacokinetics and pharmacodynamics; Schröppel B contributed to the literature context and manuscript preparation; Ludwig U contributed to the clinical relevance and practical applicability.
Conflict-of-interest statement: There is no conflict of interest with any financial organization regarding the material discussed in the manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Frieder Keller, MD, Section of Nephrology, Department of Internal Medicine 1, Center for Internal Medicine, University Hospital, Albert-Einstein-Allee 23, D-89070 Ulm, Germany. frieder.keller@uni-ulm.de
Telephone: +49-731-50044561 Fax: +49-731-50044567
Received: November 27, 2014
Peer-review started: November 28, 2014
First decision: December 26, 2014
Revised: January 12, 2015
Accepted: May 5, 2015
Article in press: May 6, 2015
Published online: July 6, 2015
Processing time: 220 Days and 22.8 Hours
Abstract

Patients with cancer have a high inherent risk of infectious complications. In addition, the incidence of acute and chronic kidney dysfunction rises in this population. Anti-infective drugs often require dosing modifications based on an estimate of kidney function, usually the glomerular filtration rate (GFR). However, there is still no preferential GFR formula to be used, and in acute kidney injury there is always a considerable time delay between true kidney function and estimated GFR. In most cases, the anti-infective therapy should start with an immediate and high loading dose. Pharmacokinetic as well as pharmacodynamic principles must be applied for further dose adjustment. Anti-infective drugs with time-dependent action should be given with the target of high trough concentrations (e.g., beta lactam antibiotics, penems, vancomycin, antiviral drugs). Anti-infective drugs with concentration-dependent action should be given with the target of high peak concentrations (e.g., aminoglycosides, daptomycin, colistin, quinolones). Our group created a pharmacokinetic database, called NEPharm, hat serves as a reference to obtain reliable dosing regimens of anti-infective drugs in kidney dysfunction as well as renal replacement therapy. To avoid the risk of either too low or too infrequent peak concentrations, we prefer the eliminated fraction rule for dose adjustment calculations.

Keywords: Anti-infective drugs; Cancer; Kidney function; Pharmacodynamics; Pharmacokinetics; Dose adjustmen; NEPharm

Core tip: Cancer patients are at an increased risk for both infection and kidney dysfunction. Infections need immediate treatment; during the further course, kidney function must be taken into account. Almost any drug can be adjusted to any kidney function in every patient. Observation of the pharmacokinetic principles allows avoiding adverse events. Observation of the pharmacodynamic principles is needed to obtain anti-infective success. The target concentration for anti-infective drugs with a concentration-dependent effect is the high peak level. The target concentration for anti-infective drugs with a time-dependent effect is the high trough level. When in doubt, the peak should be the target.