Mechanism Of Action
Akten™ (lidocaine hydrochloride ophthalmic gel) is a local anesthetic agent that stabilizes the neuronal membrane
by inhibiting the ionic fluxes required for the initiation and conduction of
impulses, thereby effecting local anesthetic action. Anesthesia generally occurs
between 20 seconds to 1 minute and persists for 5 to 30 minutes.
Lidocaine may be absorbed following topical administration to mucous membranes.
Its rate and extent of absorption depend upon various factors such as concentration,
the specific site of application, viscosity of the agent, and duration of exposure.
The plasma binding of lidocaine is dependent on drug concentration, and the
fraction bound decreases with increasing concentration. At concentrations of
1 to 4 mcg of free base per mL, 60 to 80 percent of lidocaine is protein bound.
Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein.
Lidocaine is metabolized rapidly by the liver, and metabolites and unchanged
drug are excreted by the kidneys. Biotransformation includes oxidative Ndealkylation,
ring hydroxylation, cleavage of the amide linkage, and conjugation. N-dealkylation,
a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide
and glycinexylidide. The pharmacologic/toxicologic actions of these metabolites
are similar to, but less potent than, those of lidocaine. Approximately 90%
of lidocaine administered is excreted in the form of various metabolites, and
less than 10% is excreted unchanged. The primary metabolite in urine is a conjugate
of 4-hydroxy-2, 6-dimethylaniline.
Studies of lidocaine metabolism following intravenous bolus injections have
shown that the elimination half-life of this agent is typically 1.5 to 2 hours.
Because of the rate at which lidocaine is metabolized, any condition that affects
liver function may alter lidocaine kinetics. The half-life may be prolonged
twofold or more in patients with liver dysfunction. Renal dysfunction does not
affect lidocaine kinetics but may increase the accumulation of metabolites.
The effect of Akten™ (lidocaine hydrochloride ophthalmic gel) on ocular anesthesia was studied in a multi-center,
randomized, controlled, double-blind study.
A total of 209 subjects were enrolled, with 54, 51, 53, and 51 subjects randomized
to the sham, Akten™ (lidocaine hydrochloride ophthalmic gel) 1.5%, Akten™ (lidocaine hydrochloride ophthalmic gel) 2.5%, and Akten™ (lidocaine hydrochloride ophthalmic gel) 3.5% groups,
respectively. Ocular anesthesia was achieved within 5 minutes of anesthetic
application by 47 of 51 subjects (92%) in the Akten™ (lidocaine hydrochloride ophthalmic gel) 3.5% group.
The mean time to anesthesia onset ranged from 20 seconds to 5 minutes was not
affected by Akten™ (lidocaine hydrochloride ophthalmic gel) dose. The mean time to anesthesia onset was approximately
60 seconds, with a median onset time of 40 seconds for the Akten™ (lidocaine hydrochloride ophthalmic gel) 3.5%
group. Among the subjects in the Akten™ (lidocaine hydrochloride ophthalmic gel) groups who achieved anesthesia
within 5 minutes, approximately 90% had achieved anesthesia within 60 seconds
The duration of anesthesia generally ranged from approximately 5 minutes to
30 minutes, with mean anesthesia durations of approximately 15 minutes for the
Akten™ (lidocaine hydrochloride ophthalmic gel) 3.5% group.
Approximately 84% of the subjects in the Akten™ (lidocaine hydrochloride ophthalmic gel) 3.5% group experienced
anesthesia for at least 5 minutes, approximately 55% of subjects experienced
anesthesia for 10 minutes or longer and 27% experienced anesthesia for 15 minutes
or longer. The anesthetic effect of additional applications of Akten™ (lidocaine hydrochloride ophthalmic gel)
has not been evaluated.