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) = (R/sub T/(t) - R/sub R/(t))/(1 - R/sub R/(t)), where R/sub T/ and R/sub R/ 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 < 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.