Ketamine effects on bupivacaine local anaesthetic activity and pharmacokinetics of bupivacaine in mice.
This study was designed to document possible changes in bupivacaine (B) local anaesthetic activity and pharmacokinetics in mice after a ketamine (K) injection. In the experiments, bupivacaine (8.25 mg.kg(-1)), was injected into the popliteal space of the right posterior limb: the local anaesthetic activity was assessed according to a sciatic nerve blockade method with three different doses (2, 10 and 40 mg/kg) of ketamine and the kinetics were studied after a 10 mg/kg dose. When ketamine was associated, the local anesthetic activity of bupivacaine was significantly enhanced as well as its elimination half-life. Significantly lower levels of the main metabolite, PPX, were observed, when ketamine was associated, suggesting a metabolic inhibition phenomenon. The ketamine-induced increase in the total anaesthetic effect of bupivacaine may thus be explained by kinetic modifications i.e. a possible inhibiting effect of ketamine on the metabolism of bupivacaine.
Gantenbein
M
M
Laboratoire de Pharmacologie Médicale, Faculté de Médecine de Marseille, France.
Abat
C
C
Attolini
L
L
Pisano
P
P
Emperaire
N
N
Bruguerolle
B
B
D000772:Anesthesia, Local; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000493:pharmacokinetics*; D000818:Animals; D002045:Bupivacaine / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006207:Half-Life; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice
D000778:Anesthetics, Dissociative; D000779:Anesthetics, Local; D007649:Ketamine; D002045:Bupivacaine