THE RELATIONSHIP BETWEEN ALFENTANIL DISTRIBUTION KINETICS AND CARDIAC-OUTPUT

The relationship between cardiac output and the tissue distribution of alfentanil was investigated in seven healthy volunteers. Subjects were given 10-mu-g/kg alfentanil and 0.5 mg/kg indocyanine green. Arterial blood samples were obtained at baseline, 1 minute, every 1/2 minute until 5 minutes, and then every minute until 15 minutes after the drug injection was begun. Subsequent samples were collected to 6 hours. Cardiac output was measured continuously by use of thoracic bioimpedance. Alfentanil pharmacokinetics were modeled with both a standard three-compartment model and a four-compartmental model based in part on the two-compartmental pharmacokinetics of indocyanine green. The sum of intercompartmental clearances for both the three- and four-compartment models were significantly correlated with the measured cardiac outputs, r = 0.93 and r = 0.88, respectively. These findings indicate that the intercompartmental clearance (i.e., tissue distribution) of alfentanil is largely determined by cardiac output (i.e., tissue blood flow).