Pharmacokinetics of tin‐mesoporphyrin in man and the effects of tin‐chelated porphyrins on hyperexcretion of heme pathway precursors in patients with acute inducible porphyria

Abstract

Tin‐mesoporphyrin shares many of the properties of its parent compound, tin‐protoporphyrin. These include competitive inhibition of heme oxygenase, amelioration of jaundice and suppression of chemically induced hepatic porphyria. Tin‐mesoporphyrin is cleared from the plasma of normal subjects with dose‐dependent pharmacokinetics (T1/2 = 3.8 hr following i.v. administration of 1 μmole per kg body weight), and small amounts (<1% of administered dose) are excreted into the urine and feces. Intramuscular administration of tin‐mesoporphyrin resulted, within 2 hr, in plasma concentrations identical to those obtained following i.v. administration, but the compound was not absorbed orally. The only dose‐limiting side effect was transient cutaneous photosensitivity. High doses (1 μmole per kg body weight) of tin‐mesoporphyrin resulted in significant decreases in plasma bilirubin concentrations at 24 and 48 h after treatment of normal subjects. Administration of both tin‐protoporphyrin and tin‐mesoporphyrin resulted in decreases in the urinary excretion of heme pathway intermediates in stable hyperexcreters with acute hepatic porphyria. Copyright © 1989 American Association for the Study of Liver Diseases