Effect of potassium ethylxanthogenate on the toxicity and analgesic effect of acetaminophen.
The effect of potassium ethylxanthogenate (PEX) on the toxicity and the analgesic effect of acetaminophen (AAP) were investigated on male albino mice. PEX in a dose of 80 mg/kg body weight, administered subcutaneously or orally one hour before AAP, or simultaneously with it, induces prolongation of the survival of the experimental animals and increases LD50 of AAP. The protective effect of PEX (s.c. and p.o.) is more pronounced when this agent is introduced one hour before AAP (i.p. and p.o.), compared with the simultaneous administration, and when it is applied orally, compared with the subcutaneous administration. The average lethal dose of the combination (AAP p.o. + PEX p.o. 1 hour previously) increases 2.57 times after observation for 7 days, compared with that of AAP. Although it does not possess its own analgesic effect, PEX potentiates the analgesic effect of AAP (which is more pronounced for the low AAP doses) and reduces its average effective dose. After 14-day administration, AAP potentiates its own analgesic effect in the lower doses. The potentiating effect of PEX on the analgesic effect of AAP is similar on the first and on the 14th day of the treatment. The principal mechanism through which PEX decreases the toxicity and potentiates the analgesic effect of AAP is assumed to be the inhibition of its metabolism by inhibition of the cytochrome P-450-linked monooxygenases, not ruling out the possibility of a certain effect on the AAP absorption.
Dimova
S
S
Institute of Physiology, Bulgarian Academy of Sciences.
Stoytchev
T
T
D000082:Acetaminophen / Q000494:pharmacology* / Q000633:toxicity; D000700:Analgesics; D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D013871:Thiones / Q000494:pharmacology*
D000700:Analgesics; D065607:Cytochrome P-450 Enzyme Inhibitors; D013871:Thiones; D000082:Acetaminophen; C004918:ethylxanthate; D006899:Mixed Function Oxygenases