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.
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.
Galbraith
R A
RA
Rockefeller University Hospital, New York, New York 10021.
Kappas
A
A
D000208:Acute Disease; D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D006418:Heme / Q000378:metabolism*; D006801:Humans; D007273:Injections, Intramuscular; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008665:Metalloporphyrins / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D008875:Middle Aged; D010787:Photosensitivity Disorders / Q000139:chemically induced; D011164:Porphyrias / Q000378:metabolism*; D011166:Porphyrins / Q000494:pharmacology*; D011524:Protoporphyrins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*
D008665:Metalloporphyrins; D011166:Porphyrins; D011524:Protoporphyrins; C055421:tin mesoporphyrin; D006418:Heme; C032628:tin protoporphyrin IX