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Assessing Physostigmine Efficacy by Response Surface Modeling: A Comparison to Pyridostigmine Efficacy

Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia.

R. A. Carchman

Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia.

W. H. Carter, Jr.

Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia.

E. D. Campbell

Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia.

R. M. Boyle

Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia.

J. G. Staniswalis

Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia.

D. E. Jones

Comparative Toxicology Labs, Kansas State University, Manhatten, Kansas.

F. M. Reid

ATSDR, Atlanta, Georgia.

I. Koplovitz

USAMRICD, Aberdeen Proving Ground, Maryland.

The therapeutic efficacy of atropine sulfate/pralidoxime chloride (ATR/2-PAM) treatment therapy and physostigmine (PHY) pretreatment therapy was evaluated in soman-challenged guinea pigs. Response surface analysis (RSM) of treatment efficacy indicated that the optimal ATR/2-PAM dose combination varied as a function of both the soman (GD) challenge level and the PHY pretreatment dose. Efficacy was, therefore, evaluated for varying PHY pretreatment doses in combination with the appropriate optimal ATR/2-PAM treatment (as determined by RSM for each soman challenge dose and PHY dose evaluated). The response surfaces depicting the effects (i.e., probability of survival) of ATR/2-PAM combinations at fixed levels of PHY and GD are presented, and confidence regions and point estimates for optimal ATR/2-PAM treatment combination are included. It was estimated that with optimal therapy a protective ratio (PR) of 6 can be observed. Comparisons were made between the use of PHY/ATR/2-PAM as presented here and the use of PYR/ATR/2-PAM, as discussed by Jones et al.⁽¹⁾ Both studies showed a strong positive (r 0.98) relationship between dose and the PR. However, the estimated slope parameter for PHY was significantly larger (P < 0.001) than the slope parameter for pyridostigmine (PYR). This difference in slopes may indicate different mechanisms of action for PYR and PHY.

International Journal of Toxicology, Vol. 7, No. 7, 1013-1030 (1988)
DOI: 10.3109/10915818809014530


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