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Determination of the falloff constant (k $_{ f }$) from modeling biochemical marker release : A new variable for discriminating therapies

Cardiovascular Toxicology : Volume 1, Issue 1, March 2001

Determination of the falloff constant (k $_{ f }$) from modeling biochemical marker release : A new variable for discriminating therapies

Content Provider	Springer Nature Link
Author	Christenson, Robert H. Duh, Show Hong Roe, Mathew T. Ohman, E. Magnus
Copyright Year	2001
Abstract	A new variable termed the falloff constant (k $_{ f }$) was derived from the curve fitting of serial CK-MB measurements. k $_{ f }$ represents the rate constant of maximal decline in serum CK-MB and is determined from the slope of the lognormal curve at the inflection point. Physiologically, k $_{ f }$ /′s magnitude reflects the balance between CK-MB's rate of release from tissue and the rate of elimination.We examined k $_{ f }$ in two myocardial infarction (MI) patient sets. The first set was homogeneous and taken from the TAMI 7 study (n=147) and included 111 patients having TIMI 2–3 flow after thrombolytic therapy and 36 patients who initially had TIMI 0–1 flow. The TIMI 0–1 patients were opened to TIMI 3 by angioplasty within 3 h. The second set consisted of 196 patients enrolled in the IMPACT-AMI study that demonstrated the efficacy of the glycoprotein (GP) IIb/IIIa antagonist eptifibatide. This second set consisted of 93 patients in the GP IIb/IIIa treatment group and 103 in the placebo group. Log-normal curve-fitting parameters including peak maximum and curve area were also compared to k $_{ f }$ in the GP IIb/IIIa versus placebo set.The Wilcoxon test showed no difference between the two groups of TAMI 7 patients (p=0.22). However, there was a highly significant difference in k $_{ f }$ between the GP IIb/IIIa treatment group versus the placebo group (p=0.0014). Both k $_{ f }$ and peak maximum from curve fitting showed significant differences between the GP IIb/IIIa treatment group and the placebo group; however, k $_{ f }$ showed a substantially lower p-value (p=0.0014 and p=0.023, respectively).As expected, k $_{ f }$ showed no difference between the TAMI 7 groups because this was a homogeneous patient set in that they all had TIMI 3 patency status within 3 h of treatment. However, in the patient set having very different treatments, GP IIb/IIIa versus placebo, there was a highly significant difference in the k $_{ f }$ variable. These data suggest that differences in reperfusion are reflected by k $_{ f }$ and that this variable may represent a valuable new nonmortality end point derived from curve fitting analysis.
Starting Page	171
Ending Page	176
Page Count	6
File Format	PDF
ISSN	15307905
Journal	Cardiovascular Toxicology
Volume Number	1
Issue Number	2
e-ISSN	15590259
Language	English
Publisher	Humana Press
Publisher Date	2001-01-01
Publisher Place	Totowa
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Log-normal curve fitting CK-MB reperfusion falloff constant Pharmacology/Toxicology Cardiology
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Toxicology Cardiology and Cardiovascular Medicine

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