Pharmacokinetics and pharmacodynamics of oximes in unanesthetized pigs.
The pharmacokinetics and cardiovascular pharmacodynamics of two oximes were studied in unanesthetized pigs. Effects of 2-[(hydroxyimino)methyl]-1-methylpyridinium chloride (pralidoxime chloride; 2-PAM Cl; 50 mumol/kg) were compared with those of 1,1-methylene bis[4(hydroxyiminomethyl) pyridinium] dichloride (methoxime; MMB-4; 100 mumol/kg). Cardiopulmonary 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 Cl 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.
Stemler
F W
FW
United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425.
Tezak-Reid
T M
TM
McCluskey
M P
MP
Kaminskis
A
A
Corcoran
K D
KD
Shih
M L
ML
Stewart
J R
JR
Wade
J V
JV
Hayward
I J
IJ
D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D001784:Blood Gas Analysis; D001831:Body Temperature / Q000187:drug effects; D002801:Cholinesterase Reactivators / Q000493:pharmacokinetics / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D008954:Models, Biological; D010091:Oximes / Q000493:pharmacokinetics* / Q000494:pharmacology; D011220:Pralidoxime Compounds / Q000493:pharmacokinetics / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects*; D013552:Swine
D002801:Cholinesterase Reactivators; D010091:Oximes; D011220:Pralidoxime Compounds; C005514:N,N'-monomethylenebis(pyridiniumaldoxime); D000110:Acetylcholinesterase; C028797:pralidoxime