We calculated an ED50 of 8.1 μg/kg (0.7
nmol/kg) for recombinant human pre-elafin. Beside elafin, we did not
directly compare pre-elafin to other neutrophil elastase proteinaceous
inhibitors. Using exactly the same model, others have determined an
ED50 of 35 μg/kg (6.3 nmol/kg) for truncated
SLPI,27 which represents a ninefold higher dose than
pre-elafin on a molar basis. In a similar model, in whichα
1-antitrypsin was administered via the same
route but 5 min prior to neutrophil elastase,
others,26,28,33 consistently showed an
ED50 of approximately 2.85 mg/kg (54.8 nmol/kg).
This represents a 78-fold higher dose than pre-elafin on a molar basis.
It has been suggested,26 that low-molecular-weight
synthetic inhibitors would have an advantage over proteinaceous
inhibitors. However, recombinant human pre-elafin appears to be 30-fold
to 120-fold more potent on a molar basis (twofold to sixfold more
potent on a weight basis) than small synthetic inhibitors (molecular
weight, 541 to 1,166 d) such as FK706, FR134043, FR901277, and
TEI-8362, based on published studies26,28,33–34 using a
similar experimental model. Therefore, the potency of recombinant human
pre-elafin to inhibit neutrophil elastase-induced lung hemorrhage
compares more than favorably to the potency of other neutrophil
elastase inhibitors either proteinaceous or synthetic.