Pharmacokinetics and Pharmacodynamics of Oximes in Unanesthetized Pigs

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.