Comparative Efficacy of Oral Calcitonin-Gene-Related Peptide Antagonists for the Treatment of Acute Migraine: Updated Meta-analysis.

BACKGROUND AND OBJECTIVE: The calcitonin gene-related peptide (CGRP) is a new therapeutic target in migraine-a common disorder resulting in reduced quality of life. The aim of this study was to compare the clinical efficacy of five oral CGRP antagonists with that of a placebo and triptans against acute migraine via meta-analysis. METHODS: Suitable randomized controlled trials (RCTs) were searched in PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (WHO-ICTRP) to compare the efficacy of oral CGRP antagonists with that of a placebo and triptans against acute migraine. Review Manager 5.4 was used for data analysis. RESULTS: A total of 17 trials met the eligibility criteria and were studied in detail. The CGRP antagonists were significantly more effective than the placebo with respect to outcomes such as pain freedom at 2 h post-dose (odds ratio = 2.11; 95% confidence intervals [CIs] = 1.90-2.35) and pain relief at 2 h post-dose (odds ratio = 1.94; 95% CIs = 1.70-2.21). Similar results were found in the subgroup analysis conducted to compare the clinical efficacy of the FDA-approved oral CGRP antagonists (ubrogepant and rimegepant) and placebo. However, the CGRP antagonists were less effective than the triptans with respect to outcomes such as pain freedom at 2 h post-dose (odds ratio = 0.66; 95% CIs = 0.55-0.78) and pain relief at 2 h post-dose (odds ratio = 0.78; 95% CIs = 0.66-0.93). CONCLUSION: CGRP antagonists are more effective than placebo against acute migraine; however, further studies are required to consider CGRP antagonists as standard first-line treatment for acute migraine instead of triptans, especially in patients with co-existing cardiovascular diseases.

Interspecies differences on pharmacokinetics of rebamipide following oral administration to rats and dogs.

Rebamipide is used widely in East Asia for the treatment of gastric ulcers, acute gastritis, and exacerbated chronic gastritis. The objective of this study was to investigate the pharmacokinetic (PK) properties of rebamipide following single oral administration in rats and dogs. Eleven rats and dogs received single oral administrations of rebamipide (35 mg/kg and 100 mg, respectively). Blood samples were collected according to the assigned schedule, and the plasma concentration of rebamipide was determined using liquid chromatography-tandem mass spectrometry. A double-peak phenomenon was observed in the PK profile of rebamipide in rats. In contrast, rebamipide showed a conventional PK profile without double peaks in dogs. The half-life of rebamipide in rats (12.85 ± 7.86 h) was longer than that in dogs (5.62 ± 2.24 h), and the apparent total clearance (Clt /F) of rebamipide in rats (3.32 ± 1.18 L/h) was lower than that in dogs (105.01 ± 42.37 L/h). Simple allometric approaches showed that the correlation between body weight and Clt /F (R2 = 0.9287) among rats, dogs, and humans appeared satisfactory. This finding will help not only in understanding the pharmacology of rebamipide but also in establishing a strategy for in vivo evaluation of novel rebamipide formulations.