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Stannsoporfin

Description of Stannsoporfin: Stannsoporfin (SnMP) is a porphyrin-Sn(IV) complex, is also a  potent heme oxygenase inhibitor, that inhibits HO-1–mediated heme catabolism with potential medicinal application  for the treatment of  both neonatal jaundice and inherited hyperbilirubinemia syndromes. It was developed to possess unique structural and photophysical properties that make it a particularly potent and bioavailable in vivo inhibitor suitable for clinical use in newborns and studies to date have revealed a very favorable therapeutic profile with no significant adverse side effects.  (source: J Immunol. 2010 Nov 1;185(9):5279-88.)

Tin mesoporphyrin (SnMP) has emerged as a potential agent for reducing total bilirubin concentrations in preterm newborns. Adverse effects associated with SnMP use include photosensitization (which complicates its use in conjunction with phototherapy), and potential inhibition of several other enzymes that have essential roles in metabolism. Clinical studies of SnMP have shown that it prevents excessive neonatal hyperbilirubinemia and reduces the need for neonatal phototherapy in term and near-term infants. Because further research, specifically safety investigations, are complicated, use of SnMP should be reserved for neonates who are at especially high risk for developing bilirubin-induced neurologic dysfunction or participating in clinical trials. [source: NeoReviews (2007) 8, 77-84]

Tin-mesoporphyrin (SnMP) is a competitive inhibitor of microsomal heme oxygenase (the rate-limiting enzyme in the heme catabolic pathway). It was administered as a single intramuscular dose at 46 hours of life to a very-low-birth-weight infant with severe hemolytic hyperbilirubinemia who had been awaiting an exchange transfusion. This case documents the effective elimination of the need for an exchange transfusion in a very-low-birth-weight infant and is a confirmation of the experience of others for the use of SnMP in reducing bilirubin production.

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1: Burt TD, Seu L, Mold JE, Kappas A, McCune JM. Naive human T cells are activated and proliferate in response to the heme oxygenase-1 inhibitor tin mesoporphyrin. J Immunol. 2010 Nov 1;185(9):5279-88. Epub 2010 Oct 4. PubMed PMID: 20921523.

2: Tiwari M, Chandra R, Das SK, Prakash S. Tin mesoporphyrin in conjunction with retinoic acid reverses the retinoic acid induced enhancement of phospholipase A(2) activity in vivo in rats. Artif Cells Blood Substit Immobil Biotechnol. 2007;35(3):275-85. PubMed PMID: 17573627.

3: Abate A, Zhao H, Wong RJ, Stevenson DK. The role of Bach1 in the induction of heme oxygenase by tin mesoporphyrin. Biochem Biophys Res Commun. 2007 Mar 16;354(3):757-63. Epub 2007 Jan 18. PubMed PMID: 17257585; PubMed Central PMCID: PMC1805812.

4: DeSandre GH, Wong RJ, Morioka I, Contag CH, Stevenson DK. The effectiveness of oral tin mesoporphyrin prophylaxis in reducing bilirubin production after an oral heme load in a transgenic mouse model. Biol Neonate. 2006;89(3):139-46. Epub 2005 Oct 3. PubMed PMID: 16205054.

5: Koeppen AH, Dickson AC, Smith J. Heme oxygenase in experimental intracerebral hemorrhage: the benefit of tin-mesoporphyrin. J Neuropathol Exp Neurol. 2004 Jun;63(6):587-97. PubMed PMID: 15217087.

6: Reddy P, Najundaswamy S, Mehta R, Petrova A, Hegyi T. Tin-mesoporphyrin in the treatment of severe hyperbilirubinemia in a very-low-birth-weight infant. J Perinatol. 2003 Sep;23(6):507-8. PubMed PMID: 13679941.

7: Laftah AH, Raja K, Simpson RJ, Peters TJ. Effect of Tin-mesoporphyrin, an inhibitor of haem catabolism, on intestinal iron absorption. Br J Haematol. 2003 Jul;122(2):298-304. PubMed PMID: 12846900.

8: Nalos M, Vassilev D, Pittner A, Asfar P, Brückner UB, Schneider EM, Georgieff M, Radermacher P, Froeba G. Tin-mesoporphyrin for inhibition of heme oxygenase during long-term hyperdynamic porcine endotoxemia. Shock. 2003 Jun;19(6):526-32. PubMed PMID: 12785007.

9: Martínez JC, García HO, Otheguy LE, Drummond GS, Kappas A. Treatment of hyperbilirubinemia pharmacologic approach SnMP(tin-mesoporphyrin). J Perinatol. 2001 Dec;21 Suppl 1:S101-3; discussion S104-7. PubMed PMID: 11803428.

10: Chen Y, Zhang B, Chen JG, Huang DY. Solvent effects on the absorption and fluorescence characteristics of tin(IV) mesoporphyrin. Spectrochim Acta A Mol Biomol Spectrosc. 2001 Oct;57(12):2451-6. PubMed PMID: 11767838.

11: Wagner KR, Hua Y, de Courten-Myers GM, Broderick JP, Nishimura RN, Lu SY, Dwyer BE. Tin-mesoporphyrin, a potent heme oxygenase inhibitor, for treatment of intracerebral hemorrhage: in vivo and in vitro studies. Cell Mol Biol (Noisy-le-grand). 2000 May;46(3):597-608. PubMed PMID: 10872746.

12: Lutton JD, Jiang S, Drummond GS, Abraham NG, Kappas A. Comparative pharmacology of zinc mesoporphyrin and tin mesoporphyrin: toxic actions of zinc mesoporphyrin on hematopoiesis and progenitor cell mobilization. Pharmacology. 1999 Jan;58(1):44-50. PubMed PMID: 9831830.

13: Rubaltelli FF, Dario C, Zancan L. Congenital nonobstructive, nonhemolytic jaundice: effect of tin-mesoporphyrin. Pediatrics. 1995 Jun;95(6):942-4. PubMed PMID: 7761229.

14: Valaes T, Petmezaki S, Henschke C, Drummond GS, Kappas A. Control of jaundice in preterm newborns by an inhibitor of bilirubin production: studies with tin-mesoporphyrin. Pediatrics. 1994 Jan;93(1):1-11. PubMed PMID: 8265301.

15: Böni RE, Huch Böni RA, Galbraith RA, Drummond GS, Kappas A. Tin-mesoporphyrin inhibits heme oxygenase activity and heme-iron absorption in the intestine. Pharmacology. 1993 Nov;47(5):318-29. PubMed PMID: 8265722.

16: Cannon JB, Martin C, Drummond GS, Kappas A. Targeted delivery of a heme oxygenase inhibitor with a lyophilized liposomal tin mesoporphyrin formulation. Pharm Res. 1993 May;10(5):715-21. PubMed PMID: 8321837.

17: Galbraith RA, Drummond GS, Kappas A. Suppression of bilirubin production in the Crigler-Najjar type I syndrome: studies with the heme oxygenase inhibitor tin-mesoporphyrin. Pediatrics. 1992 Feb;89(2):175-82. PubMed PMID: 1734381.

18: Fort FL, Gold J. Phototoxicity of tin protoporphyrin, tin mesoporphyrin, and tin diiododeuteroporphyrin under neonatal phototherapy conditions. Pediatrics. 1989 Dec;84(6):1031-7. PubMed PMID: 2531365.

19: Galbraith RA, Kappas A. 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. Hepatology. 1989 Jun;9(6):882-8. PubMed PMID: 2714739.