Pharmacokinetics of propofol administered by target-controlled infusion to alcoholic patients.

Abstract

Chronic alcoholic patients are frequently presented for anesthesia and surgery. These patients require higher doses of propofol than control patients for induction of anesthesia, but whether this is because of changes in pharmacokinetics or pharmacodynamics is not known. This study was designed to investigate the influence of chronic ethanol intake on propofol pharmacokinetics. Fifteen chronic alcoholic and 15 control patients, receiving propofol by target-controlled infusion for otolaryngologic surgery, were studied. Blood propofol concentrations were measured at regular intervals during and after the propofol infusion. Nonlinear mixed-effects population models (NONMEM) examining the influence of alcoholism were constructed. The influence of recovery on propofol pharmacokinetic parameters was also addressed. The total amount of propofol and the predicted and measured concentrations during all phases of anesthesia did not differ between the two groups. The fact that the measured concentrations at the time of opening eyes were similar further confirmed that the potency of propofol was not modified by the alcoholic status of the patients. Chronic alcoholism was associated with only mild changes in propofol pharmacokinetics (increase in rapid intercompartmental clearance and greater interindividual variability in the central volume of distribution). The rebound in concentration frequently observed during the recovery phase could be related to decreased propofol peripheral volumes of distribution despite an increase in elimination clearance. Chronic alcoholism induces only mild changes in the pharmacokinetics of propofol. Conversely, propofol pharmacokinetics are markedly different during anesthesia and surgery or after opening eyes in the recovery period.