Pulmonary extraction of C-11 chlorpromazine, measured by residue detection in man

Uptake of C-11 chlorpromazine (CPZ) was measured to evaluate the nonrespiratory function of lung in patients. A multiple-indicator dilution technique was used with external detection. Following intravenous bolus injection of C-11 CPZ, with In-113m transferrin as an intravascular reference molecule, counts were recorded with a scintillation camera using two energy windows. The residue functions, R(t), for C-11 CPZ and In-113m transferrin were plotted against time for selected areas of interest, and the CPZ area-weighted extraction, E(t), was computed for the same areas every 250 msec using the formula: E(t) = [RT(t) - RR(t)]/[1 - RR(t)], where RT and RR are the normalized residue functions for CPZ and transferrin, respectively. The initial extraction was 90 +/- 5% in four normal subjects and 64 +/- 7% in six patients with chronic obstructive lung disease (C.O.L.D.), these values being significantly different (p less than 0.001). The large initial extraction of CPZ in a single passage through the pulmonary vasculature resulted from a fixation to membranes, due to its high liposolubility. The lower extraction seen in patients with C.O.L.D. was explained by weaker fixation to lung tissue.