Racemic Ketamine and S(+)-Ketamine Concentrations in Cerebrospinal Fluid after Epidural and Intravenous Administration in Rabbits

The pharmacokinetic characteristic of ketamine, particularly the shift from the epidural space to the cerebrospinal fluid (CSF), is still unclear. Furthermore pharmacokinetic differences between racemic ketamine and S(+)-ketamine are not clearly described when administered into the epidural space. We measured plasma and CSF concentrations of racemic ketamine and S(+)-ketamine after 2 mg/kg intravenous or 2 mg/kg epidural injection in 32 rabbits, and calculated pharmacokinetic parameters by the moment analysis method. The elimination half time of S(+)-ketamine was significantly shorter than that of racemic ketamine and the systemic distribution volume of S(+)-ketamine was significantly smaller than that of racemic ketamine in the CSF. Pharmacokinetic parameters in the CSF after epidural injection of racemic versus S(+)-ketamines were: maximum concentration, 0.4 ± 0.1 versus 0.6 ± 0.2 ?g/mL (not significant); time to maximum concentration, 9.7 ± 2.1 versus 9.0 ± 3.4 min (not significant); elimination half time, 127.1 ± 25.2 versus 89.3 ± 19.4 min (P = 0.005); area under the curve, 56.4 ± 6.4 versus 56.6 ± 11.0 ?g?mL/min (not significant); and distribution volume, 19,463.5 ± 3266.1 versus 13,613.3 ± 4895.2 mL (P = 0.014), respectively. When injected intravenously, there was no significant difference in these parameters of the CSF between racemic and S(+)-ketamines. Racemic ketamine passed easily through the blood brain barrier when administered intravenously. It also shifted to the CSF through the systemic circulation, even when they were administered epidurally. S(+)-Ketamine had similar movement as racemic ketamine.