2.2 Pharmacokinetics
Systemically administered ketamine is chiefly metabolized by the
cytochrome P450 liver enzymes, initially to a much less potent
norketamine, and further to inactive hydroxynorketamines,
dehydronorketamines, and other metabolites.27,28Ketamine has a relatively low plasma protein binding (10-50%) and is
rapidly accumulated in the brain. It has a high clearance rate, with a
half-life of 2-4 hours.29,30 The excretion is
predominantly in urine, with minimal amounts (<5%) in feces.
The rate of elimination of ketamine is twice as rapid in children when
compared to adults, likely due to faster enzymatic metabolism in
children.31 This information plays a role in
determining the ketamine dosing frequency in children. Ketamine is
commonly available as a mixture of (S)- and (R)- enantiomers.
(S)-enantiomer is more potent as compared to (R)-enantiomer, with some
evidence of a more favorable safety profile.32
Due to its metabolism by cytochrome P450 enzymes, there is a potential
for drug interactions when used along with enzyme-inducer and
enzyme-inhibitor drugs. Drugs like metoclopramide and fosaprepitant,
which may at times be used in cancer patients as antiemetics, may have
drug interactions with ketamine, and caution must be exercised during
their concomitant use. Similarly, other CYP3A4 inhibitors like
clarithromycin, azole antifungals, verapamil, and inducers like
phenytoin, rifampicin, and steroids can alter ketamine
levels.33