TY - JOUR
T1 - Disposition of tin‐protoporphyrin and suppression of hyperbilirubinemia in humans
AU - Anderson, Karl E.
AU - Simionatto, Creuza S.
AU - Drummond, George S.
AU - Kappas, Attallah
PY - 1986/5
Y1 - 1986/5
N2 - Tin (Sn4+)-protoporphyrin, a potent competitive inhibitor of heme degradation to bile pigment, was cleared rapidly from plasma in normal subjects (t( 1/2 ) ~4 hours for plasma levels >5 nmol/ml, with evidence of dose-dependent pharmacokinetics at lower plasma concentrations). Small amounts were excreted promptly in urine (0.1% to 5.6%) and more gradually in feces (3.7% to 11.3%). The only dose-limiting (>1.0 μmol/kg, single dose) side effect was mild sensitivity to sunlight and long-wave ultraviolet light. Absorption after intramuscular administration was rapid, but there was no absorption after oral dosing. In bile duct-ligated rats treated with Sn-protoporphyrin, there was a substantial (approximately 50%) reduction in plasma bilirubin levels compared with levels in ligated control animals. Seven studies were carried out in four women with moderate to severe cholestasis secondary to primary biliary cirrhosis and in two men with Gilbert's syndrome. In these studies Sn-protoporphyrin (total doses of 0.25 to 2.0 μmol/kg body weight) reduced plasma bilirubin levels to a varying degree (7% to 43%) promptly after its intravenous administration.
AB - Tin (Sn4+)-protoporphyrin, a potent competitive inhibitor of heme degradation to bile pigment, was cleared rapidly from plasma in normal subjects (t( 1/2 ) ~4 hours for plasma levels >5 nmol/ml, with evidence of dose-dependent pharmacokinetics at lower plasma concentrations). Small amounts were excreted promptly in urine (0.1% to 5.6%) and more gradually in feces (3.7% to 11.3%). The only dose-limiting (>1.0 μmol/kg, single dose) side effect was mild sensitivity to sunlight and long-wave ultraviolet light. Absorption after intramuscular administration was rapid, but there was no absorption after oral dosing. In bile duct-ligated rats treated with Sn-protoporphyrin, there was a substantial (approximately 50%) reduction in plasma bilirubin levels compared with levels in ligated control animals. Seven studies were carried out in four women with moderate to severe cholestasis secondary to primary biliary cirrhosis and in two men with Gilbert's syndrome. In these studies Sn-protoporphyrin (total doses of 0.25 to 2.0 μmol/kg body weight) reduced plasma bilirubin levels to a varying degree (7% to 43%) promptly after its intravenous administration.
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U2 - 10.1038/clpt.1986.88
DO - 10.1038/clpt.1986.88
M3 - Article
C2 - 3698459
AN - SCOPUS:0022578955
SN - 0009-9236
VL - 39
SP - 510
EP - 520
JO - Clinical Pharmacology & Therapeutics
JF - Clinical Pharmacology & Therapeutics
IS - 5
ER -