Bucillamine has potential to attenuate or prevent damage during
myocardial infarction, cardiac surgery and
organ transplantation.
Bucillamine, a
cysteine derivative that contains two donatable
thiol groups, is capable of replenishing the
thiol group in
glutathione, thereby reactivating this endogenous defense against
oxidant injury.
Bucillamine rapidly enters cells by the same mechanism that normally transports the
amino acid cysteine.
Bucillamine is a more potent
thiol donor than other
cysteine derivatives: approximately 16-fold more potent than
N-acetylcysteine (
Mucomyst(R)) in vivo. In addition
bucillamine appears to have additional anti-inflammatory effects unrelated to its
antioxidant effect. Oral
bucillamine is used clinically in Asia for treatment of
rheumatoid arthritis. There is a strong preclinical evidence that
parenteral infusion of this agent is efficacious in acute settings characterized by
inflammation and oxidative stress. In an investigator-blinded, rigorous intact dog model, consisting of 90 min of coronary artery occlusion and 48 h of reperfusion,
bucillamine, given i.v. during the first 3 h of reperfusion, substantially reduced
myocardial infarct size. Livers exposed to 24 h of cold ischemia were markedly protected by
bucillamine in several
transplantation models. In Phase I human studies in normal volunteers,
bucillamine at doses up to 25 mg/kg/h i.v. for 3 h elicited no serious toxicity. On the basis of pharmacokinetic analyses of blood levels during these studies it was concluded that
bucillamine, infused at i.v. doses > or =10 mg/kg/h for 3 h to humans could be expected to be therapeutically effective in
myocardial infarction,
organ transplantation and other acute inflammatory syndromes.