Effects of endotoxin-induced lung injury on the pharmacokinetics of prostaglandin E2 and adenosine in rat isolated lung.

Endotoxin injected intraperitoneally caused leucopenia and pulmonary oedema in rats. These effects were spontaneously reversed over the 28 h after the single dose of endotoxin. The pharmacokinetics of three substrates, 14C-sucrose, 3H-prostaglandin E2 (PGE2) and 3H-adenosine, were measured in perfused lungs isolated from rats at different times after treatment with endotoxin. The efflux kinetics of radiolabel derived from sucrose and adenosine were little affected, but that from PGE2 was markedly changed. The metabolism of PGE2 was also decreased. The change in PGE2 pharmacokinetics preceded the pulmonary oedema, but both pharmacokinetics and oedema returned to normal at the same time (28 h after endotoxin). It may be feasible to use PGE2 pharmacokinetics as a biochemical index for early warning of acute lung injury caused by sepsis.