Clinical Application of Pharmacokinetics: Basis for Rational Dose Selection in a Critically Ill Patient on Renal Replacement Therapy.

Abstract

Individualizing drug dosing regimens in critically ill patients on renal replacement therapy is a challenge to clinicians as guidelines are often imprecise and specific-validated pharmacokinetic software is unavailable. A case of a septic patient on hemodialysis is presented, where a quick solution for antibiotic dose adjustment based on the application of pharmacokinetic principles was found. The dose adjustment was made in two steps-the first step was to calculate total antibiotic clearance (using the formula: total drug clearance = dialysate flow rate × fraction of unbound drug in plasma + extrarenal clearance), and the second step was to calculate maintenance dose based on target plasma concentrations in steady-state (using the formula: maintenance dose = target plasma concentration × total drug clearance × dose interval). After the doses of antibiotics were adjusted, the patient's condition gradually improved, with a drop in body temperature to normal values, a decrease in plasma levels of inflammatory parameters, and the emergence of spontaneous diuresis. The plasma concentration of vancomycin was within the recommended therapeutic range. Specific pharmacokinetic software and measuring plasma concentrations of the drugs should be used for calculation of total drug clearance and dose adjustment whenever possible. However, if unavailable, basic pharmacokinetic formulas and principles could be successfully used instead to adjust the dose in critically ill patients on hemodialysis.