Pharmacokinetic and pharmacodynamic considerations of antimicrobial drug therapy in cancer patients with kidney dysfunction

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.