Journal of Pharmacokinetics and Biopharmaceutics, Vol. 24, No. 2, 1996 Pulmonary Distribution of Alfentanil and Sufentanil Studied with System Dynamics Analysis Fred Boer, 1'4 Andreas Hoeft, 2 Martin Scholz, 2 James G. Bovill, 1 Antoin G. L. Burm, 1 and Adrie Hak 3 Received June 2, 1995---Final March 13, 1996 We applied a system dynamiesapproach to the study of the pulmonary distribution of alfentanil and sufentanil in anesthetized pigs and patients, respectively. This method allows estimation of the mean transit time through the lungs and calculation of the volume of distribution of alfentanil in the lungs. In the first part of the study the pulmonary distribution of alfentanil was studied in six anesthetizedpigs during three hemodynamic states (control, partial clamping of the inferior vena cave, and complete clamping of the right pulmonary artery). In the secondpart of the study the pulmonary distribution of sufentanil was studied in 10 patients, scheduledfor elective CABG, during and after a constant rate infusion of lO min. Pulmonarypassage of the opioids was charac- terized by functions of transit times, derivedfrom the pulmonary arterial and systemic arterial concentration curves. Pulmonary distribution volumes were calculated from the mean transit time and pulmonary bloodflow. Pulmonary distribution volume of alfentanil during the control measurement was significantly higher (4864-88 ml) than during either partial caval clamping (3464-89ml, p<O.05) or right pulmonary artery clamping (336=k56ml, p<O.05). There was no change in the extravascular volume of distribution of alfentanil with each hemodynamic state. Pulmonary volume of distribution of sufentanil in the patients was 22.6 (10.9) L. Pulmonary distribution of opioids can be studied using system dynamics analysis, both after bolus injection and during and after infusion. This method can be usedfor periods beyond the initial passage of the drug through the lungs. KEY WORDS: alfentanil; sufentanil; lung metabolism; pharmacokinetic tissue distribution; indocyanine green; humans; pigs; convolution analysis. INTRODUCTION The lungs are potential sites of first-pass retention and possibly of metabolism of drugs administered intravenously. Most drugs are, however, 1Department of Anaesthesioiogy, University Hospital Leiden, P.O. Box 9600, 2300 RC Leiden, The Netherlands. 2Department of Anaesthcsiology, Reanimation and Critical Care, University Hospital G6t- tingen, Robert Kochstrasse 40, D3400 G6ttingen, Germany. 3Department of Clinical Chemistry, University Hospital Leiden, P.O. Box 9600, 2300 RC Leiden, The Netherlands. 41"o whom correspondence should be addressed. 197 0090-466x/96/0400-0197509.50/0 9 1996 plenum Publishing Corporation