Targeting of heme oxygenase inhibitors to the spleen markedly increases their ability to diminish bilirubin production.
Incorporation of heme oxygenase inhibitors into phosphatidyl choline liposomes markedly enhanced localization of these agents within the spleen as compared with the localization observed following their administration in aqueous vehicle. The increased concentration of inhibitor within splenic microsomes led to a near complete and sustained blockade of heme oxygenase activity and thus to a marked diminution in biliary bilirubin output. These studies suggest that heme oxygenase inhibitors administered within liposomes may so effectively block bilirubin production in the human newborn that ancillary methods for treating this important clinical problem may be reduced to a minimum.
Landaw
S A
SA
Rockefeller University Hospital, New York, NY 10021.
Drummond
G S
GS
Kappas
A
A
D000818:Animals; D001663:Bilirubin / Q000096:biosynthesis*; D004337:Drug Carriers; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D008081:Liposomes; D008099:Liver / Q000032:analysis / Q000201:enzymology; D008297:Male; D008665:Metalloporphyrins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D011166:Porphyrins / Q000008:administration & dosage*; D011524:Protoporphyrins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000032:analysis / Q000201:enzymology / Q000378:metabolism*; D014018:Tissue Distribution
D004337:Drug Carriers; D008081:Liposomes; D008665:Metalloporphyrins; D011166:Porphyrins; D011524:Protoporphyrins; C055421:tin mesoporphyrin; C032628:tin protoporphyrin IX; D006899:Mixed Function Oxygenases; D006419:Heme Oxygenase (Decyclizing); D001663:Bilirubin