THE PHARMACOKINETICS OF ACETYL STARCH AS A PLASMA-VOLUME EXPANDER IN PATIENTS UNDERGOING ELECTIVE SURGERY

Acetyl starch (ACS) is a new synthetic colloid solution for plasma vol ume expansion and is now undergoing phase 2 clinical trials. We compar ed the pharmacokinetics of ACS with those of hydroxyethyl starch (HES) in 32 patients (ASA physical status I and II) undergoing elective sur gery. Ln this randomized, double-blind trial, patients received either 15 mL/kg ACS 6% (average molecular weight [Mw] 200,000/molar substitu tion [MS] 0.5) or HES 6% (Mw 200,000/MS 0.5) IV up to a maximal dose o f 1000 mt. Plasma colloid concentrations were measured by repetitive a rterial blood sampling over 2 1.5 h. Plasma colloid concentrations wer e detected using a high-pressure liquid chromatography controlled enzy matic test. Standard pharmacokinetics were calculated, including initi al half-life (t(1/2init)), i.e., the time required for a 50% decline o f the maximal plasma colloid concentration at the end of drug infusion . Whereas HES was eliminated by second-order kinetics, ACS followed fi rst-order characteristics. In the first hours after IV administration, t 1/2init and clearances were similar in both groups. However, the te rminal half-life of HES was significantly longer than that of ACS (9.2 9 +/- 1.43 h vs 4.37 +/- 1.06 h). After 16.5 and 24.5 h, ACS showed si gnificantly lower plasma concentrations than HES, which indicates that the final degradation of ACS by esterases and amylase was significant ly more rapid. ACS might be an alternative plasma volume expander, whi ch avoids the accumulation of persisting macromolecules. Implications: We studied the pharmacokinetics of acetyl starch, a newly developed c olloid solution for plasma volume substitution compared with hydroxyet hyl starch in 32 surgical patients undergoing elective major general s urgical procedures. In contrast to hydroxyethyl starch, this new agent undergoes rapid and nearly complete enzymatic degradation.