Abstract
To investigate the in vivo whole blood metabolic clearance rates and sites of metabolism of prostaglandins A1 and E1 in man, constant infusions of the tritiated compounds were administered to normal subjects and to patients undergoing cardiac catheterization. The whole blood metabolic clearance rate of [3H]prostaglandin A1 in eight men was 5,003 +/- 864 liters/day (SD) or 2,546 +/- 513 liters/day per m2 (SD). Nonradioactive prostaglandin A1 was similarly infused in two subjects, and the metabolic clearance rates were determined, utilizing a specific radioimmunoassay. The clearance rates with this method correlated closely with those determined by the isotope infusions. Extraction studies of prostaglandin A1 showed that pulmonary, splanchnic, renal, and extremity perfusions resulted in 8.1 +/- 4.1, 56.1 +/- 10.1, 50.3 +/- 3.4, and 34.4 +/- 5.9% (SEM) removal, respectively. With [3H]=prostaglandin E1, the whole blood metabolic clearance rate was determined from the pulmonary artery concentration in three patients and averaged 4,832 +/- 1,518 liters/day (SD) or 2,686 +/- 654 liters/day per m2 (SD). Pulmonary extraction was 67.8 +/- 6.8% (SEM) and extremity removal averaged 6.6 +/- 4.9% (SEM). These results indicate that A prostaglandins are metabolized by several organs, such as the liver and kidney, and possibly by intravascular pathways as well. In man, the E prostaglandins are primarily metabolized by the lung, but extraction is not complete and approximately one-third may escape lung metabolism. Thus, these findings suggest that both E and A prostaglandins in the venous circulation may reach the systemic circulation in man.