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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 mumole per kg body weight), and small amounts (less than 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 mumole 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.
AuthorsR A Galbraith, A Kappas
JournalHepatology (Baltimore, Md.) (Hepatology) Vol. 9 Issue 6 Pg. 882-8 (Jun 1989) ISSN: 0270-9139 [Print] United States
PMID2714739 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Metalloporphyrins
  • Porphyrins
  • Protoporphyrins
  • tin mesoporphyrin
  • Heme
  • tin protoporphyrin IX
Topics
  • Acute Disease
  • Adult
  • Dose-Response Relationship, Drug
  • Female
  • Heme (metabolism)
  • Humans
  • Injections, Intramuscular
  • Liver Diseases (metabolism)
  • Male
  • Metalloporphyrins (adverse effects, pharmacokinetics, pharmacology)
  • Middle Aged
  • Photosensitivity Disorders (chemically induced)
  • Porphyrias (metabolism)
  • Porphyrins (pharmacology)
  • Protoporphyrins (adverse effects, pharmacokinetics, pharmacology)

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