DECREASED HEPATIC-CLEARANCE OF CLINDAMYCIN IN CRITICALLY ILL PATIENTS WITH SEPSIS

  • 1 February 1987
    • journal article
    • research article
    • Vol. 6  (2) , 154-159
Abstract
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 analyzd 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 (Ckss), 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. A simple linear-regression model failed to demonstrate strong correlations between AUC, AUMC, MRT, tbC, Vss, and Css and physiological variables. Most of the critically ill patients had altered hepatic clearance of clindamycin, compared with that of healthy volunteers. Because of the lack of discriminating variables for decreased clearance, however, and the fact that no toxicity is currently known to be associated with clindamycin concentrations obtained in the critically ill patients, no dosage-adjustment recommendations can be made at this time. For drugs such as clindamycin that are highly protein bound and have a low intrinsic clearance, data for healthy patients may not always be appropriate for application to critically ill patients.

This publication has 0 references indexed in Scilit: