The pharmacokinetics of ketamine is characterized by rapid onset of action, relatively short duration of action, and high lipid solubility. Ketamine half life has a pK of 7.5 at physiologic pH. Ketamine half life can be given by multiple routes: IV, TM, SC, oral, sublingual, rectal, nasal, transdermal, epidural, or intrathecal.
Peak plasma concentrations of ketamine occur within 1-3 minute after IV administration and within 5 minutes after TM injection and within 20 min after nasal application. Orally administered Ketamine half life undergoes extensive first pass metabolism, primarily via Ndemethylation, resulting in small ketamine concentrations and large nor-ketamine concentrations in blood and tissue.
The bioavailability of oral ketamine is around 20% whereas after sublingual and nasal spray the bioavailability increases to 30% and 45-50% respectively. The bioavailability of suppository is also 25-30%. Ketamine half life is not significantly bound (50%) to plasma proteins and leaves the blood rapidly to be distributed into tissues.
Initially, Ketamine half life is distributed to highly perfused tissues such as the brain, where the peak concentration may be 4 to 5 times that present in plasma. Subsequently, ketamine half life is redistributed from the brain and other highly perfused tissues to less well perfused tissues.
After the epidural administration the CSF concentration becomes higher than plasma but the concentrations of biotransformation products in CSF are smaller than those of the parent drug, however, the elimination half life remains equal.
Ketamine has a high hepatic clearance rate and a large volume of distribution. Therefore, alterations in hepatic blood flow could influence ketamine’s clearance rate. Animal studies show significant excretion of ketamine and its metabolite norketamine through the bile duct.
Therefore obstruction could increase the duration of action of ketamine. The duration of ketamine also increases in renal impairment; however, the plasma level of norketamine dose not alter much, implying its greater renal independent excretion.
The pharmacokinetic parameters of S- and R- Ketamine half life in the racemic mixture or -ketamine do not differ significantly. Statistically significant higher AUC and C(max) are found for S-norketamine compared with R-norketamine in the racemic group.