Pharmacokinetics of 2-pyridyl acetic acid, a major betahistine metabolite in healthy Indian volunteers

By Manoj Singh Tomar, Anil Patni, Sudershan Kumar, Nageshwar Rao Thudi, Sunil Kumar Dubey, Arshad Hussain Khuroo, Simrit Reyar, Rakesh Jain, Tausif Monif


Betahistine dihydrochloride is a vasodilator and most commonly used to treat the symptoms of M´eni`ere’s disease, vertigo and tinnitus. Due to the rapid metabolism of betahistine in humans, its estimation in human plasma is not possible. The only major metabolite detected in urine and plasma is 2-pyridyl acetic acid. The results of pharmacokinetic parameters in Indian volunteers have not been published before, and are presented and discussed for the first time in this article. A randomized, single dose, crossover bioequivalence study was conducted in healthy Indian volunteers to assess pharmacokinetics of 2-pyridyl acetic acid, by administering betahistine dihydrochloride tablet (24 mg) under fasting condition. 2-pyridyl acetic acid, was determined by a validated liquid chromatography/mass spectrometry method (LC-MS/MS) in human plasma with standard curve range 3.48 to 1279.12 ng/mL. The test betahistine dihydrochloride (24 mg) tablet formulationshowed bioequivalence with the respective reference betahistine dihydrochloride (24 mg) tablet formulation. However, on comparison of the pharmacokinetic parameters of the Indian volunteers with the results of previous study done on Chinese volunteers, Indian volunteers showed quite high Cmax (approximately twice) and AUC (approximately thrice) and also the deviation observed in both pharmacokinetic parameter was quite low as compared to  Chinese volunteers.


Key Words : Betahistine, 2-pyridyl acetic acid, pharmacokinetics, LC-MS/MS, Bioequivalence

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