Pharmacokinetics
The pharmacokinetics of ketamine has not been as well studied
as that of many other intravenous anesthetics. Ketamine pharmacokinetics has been
examined after bolus administration of anesthetizing doses (2 to 2.5 mg/kg),[31]
after a subanesthetic dose (0.25 mg/kg),[31]
[450]
and after continuous infusion (steady-state plasma level of 2000 ng/mL).[451]
Regardless of the dose, ketamine plasma disappearance can be described by a two-compartment
model. Table 10-1
contains
the pharmacokinetic values from bolus administration studies.[31]
Of note is the rapid distribution reflected in the relatively brief slow distribution
half-life of 11 to 16 minutes ( Fig.
10-21
). The high lipid solubility of ketamine is reflected in its relatively
large volume of distribution, nearly 3 L/kg. Clearance is also relatively high and
ranges from 890 to 1227 mL/min, which accounts for the relatively short elimination
half-life of 2 to 3 hours. The mean total-body clearance (1.4 L/min)
Figure 10-21
Simulated time course of plasma levels of ketamine after
an induction dose of 2.0 mg/kg. Plasma levels required for hypnosis and amnesia
during surgery are 0.7 to 2.2 µg/mL, with awakening usually occurring at levels
lower than 0.5 µg/mL.
is approximately equal to liver blood flow, which means that changes in liver blood
flow affect clearance. Thus, the administration of a drug such as halothane, which
reduces hepatic blood flow, decreases ketamine clearance.[452]
[453]
Low-dose alfentanil increases the volume
of
distribution and clearance of ketamine, thereby resulting in higher plasma concentrations.
In addition, alfentanil increases the distribution of ketamine into the brain.[454]
The pharmacokinetics of the two isomers is different. S-(+)-ketamine
has a larger elimination clearance and larger volume of distribution than R-(+)-ketamine
does.[455]
The S-(+)-enantiomer also appears to
be more potent in suppressing the EEG than either S-(-) or the racemic mixture.[456]
