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First‐in‐Human Study Demonstrating Pharmacological Activation of Heme Oxygenase‐1 in Humans
Author(s) -
Bharucha A E,
Kulkarni A,
Choi K M,
Camilleri M,
Lempke M,
Brunn G J,
Gibbons S J,
Zinsmeister A R,
Farrugia G
Publication year - 2010
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2009.221
Subject(s) - hemin , heme oxygenase , heme , pharmacology , oxidative stress , clinical pharmacology , placebo , albumin , chemistry , medicine , biochemistry , enzyme , pathology , alternative medicine
Heme oxygenase (HO)‐1 degrades heme and protects against oxidative stress, but it has not been pharmacologically induced in humans. In this randomized study of 10 healthy volunteers, hemin (3 mg/kg intravenously in 25% albumin) was shown to increase plasma HO‐1 protein concentration four‐ to fivefold and HO‐1 activity ~15‐fold relative to baseline at 24 and 48 h (placebo −56.41 ± 6.31 (baseline), 69.79 ± 13.00 (24 h), 77.44 ± 10.62 (48 h) vs. hemin −71.70 ± 9.20 (baseline), 1,126.20 ± 293.30 (24 h), 1,192.20 ± 333.30 (48 h)) in four of five subjects as compared with albumin alone ( P ≤ 0.03). This represents the overcoming of a fundamental hurdle to HO‐1 research in humans. Clinical Pharmacology & Therapeutics (2010) 87 2, 187–190. doi: 10.1038/clpt.2009.221