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 epidu- ral 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 in- jection in 32 rabbits, and calculated pharmacokinetic parameters by the moment analy- sis 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 param- eters in the CSF after epidural injection of racemic versus S(+)-ketamines were: maxi- mum concentration, 0.4 ± 0.1 versus 0.6 ± 0.2 µg/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 µgmL/min (not significant); and distribution volume, 19463.5 ± 3266.1 versus 13613.3 ± 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 ad- ministered 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.