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Title: Drug binding affinities and potencies are best described by a log-normal distribution and use of geometric means

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:7035200

(-)-Norepinephrine (NE) is used as an internal standard in their in vitro adrenergic assays, and the concentration of NE which produces a half-maximal inhibition of specific radioligand binding (affinity; K/sub I/), or half-maximal contractile response (potency; ED/sub 50/) has been measured numerous times. The goodness-of-fit test for normality was performed on both normal (Gaussian) or log /sub 10/-normal frequency histograms of these data using the SAS Univariate procedure. Specific binding of /sup 3/H-prazosin to rat liver (..cap alpha../sub 1/-), /sup 3/H rauwolscine to rat cortex (..cap alpha../sub 2/-) and /sup 3/H-dihydroalprenolol to rat ventricle (..beta../sub 1/-) or rat lung (..beta../sub 2/-receptors) was inhibited by NE; the distributions of NE K/sub I/'s at all these sites were skewed to the right, with highly significant (p < 0.01) deviations from normality. However, these data were better described by log-normal distributions. Similar results were obtained with ED/sub 50/'s of NE in isolated rabbit aorta (..cap alpha../sub 1/), phenoxybenzamine-treated dog saphenous vein (..cap alpha../sub 2/) and guinea pig atrium (..beta../sub 1/). The vasorelaxant potency of atrial natriuretic hormone in histamine-contracted rabbit aorta also was better described by a log-normal distribution, indicating that log-normalcy is probably a general phenomenon of drug-receptor interactions. Because data of this type appear to be log-normally distributed, geometric means should be used in parametric statistical analyses.

Research Organization:
Abbott Labs., Abbott Park, IL
OSTI ID:
7035200
Report Number(s):
CONF-8604222-; TRN: 87-010345
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
Country of Publication:
United States
Language:
English