Pharmacokinetics of antibiotics in critically ill patients.

Differences in pharmacokinetic data of aminoglycosides, ceftazidime and ceftriaxone between intensive care patients and volunteers or patients who are less severely ill, are described. Similar differences are observed for midazolam. In severely ill patients with normal renal function a wide interpatient variability of aminoglycoside half-life (t1/2) and increased distribution volume (Vd) are observed. This results in inadequate serum levels. A pharmacokinetic approach of drug dosing, based on serum concentrations in individual patients, is advised. For ceftazidime and ceftriaxone similar changes of t1/2 and Vd are observed. Since protein binding is frequently reduced in severely ill patients, the influence of altered binding of highly bound drugs on Vd and drug clearance is discussed. As both may be increased by reduced protein binding, the change of t1/2 to be expected is unpredictable. Dosing regimens should be based on pharmacokinetic data derived from patients whose severity of disease is comparable to that of the patients to be treated.