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. The 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 propofol (4 mg/kg) and ICG (25 mg) via two semipermanent catheters in the right internal jugular vein. Arterial blood samples were obtained from the carotid artery. The ICG injection was given for measurement of intravascular recirculatory parameters and determination of differences in propofol and ICG concentration-time profiles. No other medication was given during the experiment, and the sheep were not intubated. The arterial concentration-time curves of ICG were analyzed with a recirculatory model. The pulmonary uptake and 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 (mean +/- 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 for 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-pass pulmonary kinetics of propofol concurrently. Propofol undergoes extensive uptake and first-pass elimination in the lungs.