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

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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.

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