A study on the influence of ethanol on the toxicokinetics of ketamine in rabbits / 中国法医学杂志

ABSTRACT

Objective To investigate the influence of ethanol on the toxicokinetic profiles of ketamine and its main metabolite norketamine in rabbits.Methods Ketamine hydroehloride Wills administered orally to the rabbits at a dose of 15mg/kg in the ketamine-treated group.Ketamine hydrochloride combined with ethanol at a dose of 15 mg/kg and 3.0g/kg respectively was administered orally to those of the ethanol-coadministration group.The serum and urine samples were collected before administration and at different time points after drug delivery.The concentrations of ketamine and norketamine were determined by GC and GC/MS.Compartment model and toxicokinetics parameters were assessed by WinNorLin program.Results The mean serum concentration-time profile of ketamine after oral administration was fitted to a two-compartment open model with first order kinetics and not affected by ethanol.The K_(10),AUC and β of ketamine in rabbits of ethanol-coadministration group increased as compared with those of ketamine-treated rabbits,while T_(1/2K_(10)),T_(1/2β),A and C_(max)decreased(P＜0.05).Meanwhile,the K01,A,B and C_(max) of norketamine,the metabolite of ketamine increased in ethanol-coadministration group and T_(1/2K01) and Tmax were lowered than those in ketaminetreated group(P＜0.05).Difference of the other toxicokinetics parameters including V/F,K_(10),K_(12),K_(21),AUC,T_(1/2K_(10)),T_(1/2α),T_(1/2β) and β were not statistically significant between two groups(P＞0.05).Conclusion Ethanol may accelerate elimination of ketamine and the metabolism of ketamine to norketamine and has little effect on the absorption of ketamine,suggesting that interaction between ethanol and ketamine should be considered in cases of co-abuse of the two drugs.