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© 1991 Oxford University Press

research-article

Pharmacokinetics and Pharmacodynamics of Oximes in Unanesthetized Pigs1

FRED W. STEMLER2, THERESA M. TEZAK-REID, MICHAEL P. MCCLUSKEY, ANDRIS KAMINSKIS, KEVIN D. CORCORAN, MING L. SHIH, JAMES R. STEWART, JOHN V. WADE and ISAAC J. HAYWARD

United States Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground, Maryland 21010-5425

Received June 29, 1990; accepted November 28, 1990

Pharmacokinetics and Pharmacodynamics of Oximes in Unanesthetized Pigs. STEMLER, F. W., TEZAK-REID, T. M., MCCLUSKEY, M. P., KAMINSKIS, A., CORCORAN, K. D., SHIH, M. L., STEWART, J. R., WADE, J. V., AND HAYWARD, I. J. (1991). Fundam. Appl. Toxicol. 16, 548–558. The pharmacokinetics and cardiovascular pharmacodynamics of two oximes were studied in unanesthetized pigs. Effects of 2-[(hydroxyimino)methyl]-l-methylpyridinium chloride (pral-idoxime chloride; 2-PAM Cl; 50 µmol/kg) were compared with those of 1,1-methylene bis[4(hydroxyiminomethyl) pyridinium] dichloride (methoxime; MMB-4; 100 µmol/kg). Cardio-pulmonary parameters were monitored and plasma concentrations of oximes were determined from arterial blood samples taken at intervals over a period of 5 hr postinjection. Plasma concentrations for both oximes were fitted to standard pharmacokinetic models using the computer program PCNONLIN. Average pharmacokinetic parameters were determined for each oxime. Only mild to moderate physiological side effects were detected following intramuscular administration. 2-PAM CI was more rapidly absorbed and distributed in the blood than MMB-4. Although the latter had a slight lag time to attain detectable levels in the blood, retention time was longer than that of 2-PAM Cl.


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