title: Meclizine metabolism and pharmacokinetics: formulation on its absorption.
abstract: 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 AUC(0-24) and AUC(0-∞) 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.
authors: Center for Advancement of Drug Research and Evaluation, College of Pharmacy, Western University of Health Science, 309E, 2nd St, Pomona, CA 91766, USA.
authors: Zhijun
authors: Z
authors: Wang
authors: Benjamin
authors: B
authors: Lee
authors: Daniel
authors: D
authors: Pearce
authors: Shuai
authors: S
authors: Qian
authors: Yanfeng
authors: Y
authors: Wang
authors: Qizhi
authors: Q
authors: Zhang
authors: Moses S S
authors: MS
authors: Chow
mesh_terms: D000042:Absorption; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008468:Meclizine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008862:Microsomes, Liver / Q000378:metabolism; D009041:Motion Sickness; D011994:Recombinant Proteins / Q000378:metabolism; D012996:Solutions; D013607:Tablets; D055815:Young Adult
chemical_list: D006634:Histamine H1 Antagonists; D011994:Recombinant Proteins; D012996:Solutions; D013607:Tablets; D008468:Meclizine; D003577:Cytochrome P-450 Enzyme System