Tissue distribution and disposition of tin-protoporphyrin, a potent competitive inhibitor of heme oxygenase.

Tin(Sn)-protoporphyrin is a potent competitive inhibitor of heme oxygenase and can also suppress naturally occurring or experimentally induced hyperbilirubinemia in animals. In this study we examined the plasma clearance of Sn-protoporphyrin, its persistence in tissues and the time course of heme oxygenase inhibition up to 7 days after administration of doses up to 50 mumol/kg b.w. to adult male rats. After s.c. doses the metalloporphyrin was rapidly and almost completely absorbed. Initial plasma clearance was log-linear with a T 1/2 of approximately 3 h after either i.v. or s.c. administration. Levels of Sn-protoporphyrin in most tissues rose during the first 2 h and persisted for up to 7 days. Concentrations were highest in kidney and liver, were considerably lower in spleen, lung, intestine, adrenal and testes, and as Sn-protoporphyrin concentrations in plasma declined, concentrations in these tissues eventually exceeded simultaneous plasma concentrations. This suggests a varying degree of uptake and binding of the metalloporphyrin in these tissues. There was little or no uptake of Sn-protoporphyrin in heart, brain and red cells. Markedly decreased heme oxygenase activity in liver, kidney and spleen persisted as did Sn-protoporphyrin up to 7 days. The total amount of Sn-protoporphyrin present in tissues and excreta was a fairly constant fraction of the dose (approximately 50%) at time intervals up to 7 days after injection. These results indicate that single doses of Sn-protoporphyrin are rapidly cleared from plasma and persist in tissues and potently inhibit heme oxygenase activity for prolonged periods.