First-pass lung uptake and pulmonary clearance of propofol - Assessment with a recirculatory indocyanine green pharmacokinetic model

Background: The principal site for elimination of propofol is the liver. Th e clearance of propofol exceeds hepatic blood flow; therefore, extrahepatic clearance is thought to contribute to its elimination. This study examined the pulmonary kinetics of propofol using part of an indocyanine green (ICG ) recirculatory model. Methods: Ten sheep, immobilized in a hammock, received injections of propof ol (4 mg/kg) and ICG (25 mg) via two semipermanent catheters in the right i nternal jugular vein. Arterial blood samples were obtained from the carotid artery. The ICG injection was given for measurement of intravascular recir culatory parameters and determination of differences in propofol and ICG co ncentration-time profiles. No other medication was given during the experim ent, and the sheep were not intubated. The arterial concentration-time curv es of ICG were analyzed with a recirculatory model. The pulmonary uptake an d elimination of propofol was analyzed with the central part of that model extended with a pulmonary tissue compartment allowing elimination from that compartment. Results: During the experiment, cardiac output was 3.90 +/- 0.72 l/min (mea n +/- SD). The blood volume in heart and lungs, measured with ICG, was 0.66 +/- 0.07 1. A pulmonary tissue compartment of 0.47 +/- 0.16 1 was found fo r propofol, The pulmonary first-pass elimination of propofol was 1.14 +/- 0 .23 1/min. Thirty percent of the dose was eliminated during the first pass through the lungs. Conclusions: Recirculatory modeling of ICG allows modeling of the first-pas s pulmonary kinetics of propofol concurrently. Propofol undergoes extensive uptake and first-pass elimination in the lungs.