Meclizine Metabolism and Pharmacokinetics: Formulation on Its Absorption

Meclizine, an antihistamine, has been widely used for prophylactic treatment and management of motion sickness. However, the onset of action of meclizine was about 1 hour for the treatment of motion sickness and vertigo. A new suspension formulation of meclizine (MOS) was developed with the intention to achieve a rapid effect. To investigate the pharmacokinetics of the new MOS formulation versus the marketed meclizine oral tablet (MOT), a phase 1 pharmacokinetic study was performed in 20 healthy volunteers. In addition, an in vitro metabolic study using human hepatic microsome and recombinant CYP enzyme was also performed to determine the metabolic pathway in the human body. The plasma concentration of MOS appeared more rapidly in comparison to the MOT. The geometric mean ratios (90% confidence interval) of AUC0–24 and AUC0‐∞ indicated no significant difference in bioavailability between the 2 formulations. CYP2D6 was found to be the dominant enzyme for metabolism of meclizine, and its genetic polymorphism could contribute to the large interindividual variability. In view of the similar bioavailability with a much shorter peak time of the plasma meclizine concentration from the MOS formulation, this new formulation is expected to produce a much quicker onset of action when used for the management of motion sickness.