Acute toxicity of bupivacaine metabolites in mice.
1. This study was designed to document the acute toxicity of two metabolites of bupivacaine, desbutylbupivacaine (2,6, desbutylbupivacaine; PPX) and pipecolic acid in mice. All the compounds were administered by the intraperitoneal (i.p.) route. 2. The mean convulsant activity was 100% for controls, 30, 100, 100, 100 and 90% for 400, 200, 150, 125 and 112.5 mg/kg i.p. of PPX, respectively, and 0% for the animals receiving pipecolic acid. 3. The acute induced mortality was 60% for bupivacaine control group (50 mg/kg/i.p.), 60, 30 and 0% for 800, 400 and 200 mg/kg of pipecolic acid, respectively, and 100, 90, 60, 80 and 10% for 400, 200, 150, 125 and 112.5 mg/kg i.p. of PPX, respectively. 4. The time to convulse was 158 +/- 16 s for bupivacaine, 230 +/- 30, 270 +/- 24, 255 +/- 21, 442 +/- 84 and 418 +/- 32 s for 200, 150, 125, 112.5 and 100 mg/kg i.p. of PPX, respectively; any pipecolic acid treated animal have convulsed. 5. In conclusion, the present study demonstrated that PPX is more toxic than expected since we found that its induced mortality was approximately three times that found for bupivacaine and its CNS toxicity was about two times that of bupivacaine.
Bruguerolle
B
B
Laboratoire de Pharmacologie Médicale, Faculté de Médecine de Marseille, France.
Attolini
L
L
Gantenbein
M
M
D000818:Animals; D001711:Biotransformation; D002045:Bupivacaine / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*; D003292:Convulsants / Q000633:toxicity; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D010875:Pipecolic Acids / Q000633:toxicity
D003292:Convulsants; D010875:Pipecolic Acids; C031345:pipecolic acid; C025149:2',6'-pipecoloxylidide; D002045:Bupivacaine