Decreased hepatic clearance of clindamycin in critically ill patients with sepsis

Clindamycin pharmacokinetics was compared in critically ill patients with sepsis and healthy volunteers, and the relationship between pharmacokinetic values and physiological measurements obtained from the critically ill patients was characterized. Pharmacokinetic evaluations were performed on 10 patients with sepsis who were receiving clindamycin phosphate 900 mg i.v. every eight hours and on 6 previously studied healthy men receiving the same dosage regimen. Physiological variables measured included age, weight, cardiac index, systemic vascular resistance, central venous pressure, liver-function tests, alpha 1-acid glycoprotein concentration, and APACHE II score. Clindamycin was administered to the critically ill patients via a central venous catheter over 30 minutes; the healthy volunteers received their infusions via a peripheral venous catheter over 30 minutes. Blood samples were obtained at five minutes before and at various intervals after drug administration. Serum clindamycin concentrations were determined by a gas-liquid chromatographic method. Serum concentration data were analyzed using noncompartmental methods based on statistical moment theory, and the a priori level of significance was 0.05. The critically ill patients had significantly increased values for area under the curve (AUC), area under the moment curve (AUMC), mean residence time (MRT), and average concentration at steady state (Css), while total body clearance (TBC) was less than half that in the healthy volunteers. TBC in three of the critically ill patients was not different from that in the healthy volunteers. The apparent volume of distribution at steady state (Vss) was not significantly different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)