Revision Year: 2018
Pharmacotherapeutic group: antivertigo preparations
ATC code: N07CA01
The mechanism of action of betahistine is only partially known.
There are several hypothesis supported by animal experiments and clinical data:
Animal experiments demonstrated that betahistine pharmacodynamic properties may facilitate the therapeutic effect on the vestibular system.
Betahistine has proven efficacy in clinical trials, which included vestibular vertigo and Menière’s disease patients who showed a reduction in frequency and severity of vertigo attacks.
Following oral administration betahistine is rapidly and almost completely absorbed. It is then rapidly and almost completely metabolized to 2-pyridylacetic acid (2-PAA). Betahistine plasma levels are very low. The pharmacokinetic analysis is therefore based on the measurements of 2-PAA in the urine and plasma.
Under fed conditions Cmax is lower compared to fasted conditions. However, total absorption of betahistine is similar under both conditions, indicating that food intake only slows down the absorption of betahistine.
The percentage of betahistine that is bound by blood plasma proteins is less than 5%.
After absorption, betahistine is rapidly and almost completely metabolized into 2-PAA (which has no pharmacological activity).
After oral administration of betahistine the plasma (and urinary) concentration of 2-PAA reaches its maximum 1 hour after intake and declines with a half-life of about 3.5 hours.
2-PAA is readily excreted in the urine. In the dose range between 8 and 48mg, about 85% of the original dose is recovered in the urine. Renal or faecal excretion of betahistine itself is of minor importance.
Recovery rates are constant over the oral dose range of 8–48 mg indicating that the pharmacokinetics of betahistine are linear, and suggesting that the involved metabolic pathway is not saturated.
Adverse effects in the nervous system were seen in dogs and baboons after intravenous doses at and above 120 mg/kg.
Chronic oral toxicity testing for 18 months in rats at a dose of 500 mg/kg and 6 months in dogs at a dose of 25 mg/kg showed betahistine to be well tolerated with no definitive toxicities.
Betahistine does not have mutagenic potential.
In an 18 months chronic toxicity study in rats betahistine up to a dose of 500 mg/kg did not show any evidence for carcinogenic potential.
Effects in reproductive toxicity studies were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.
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