Bioequivalence of Rebamipide in Korean

Bioequivalence Evaluation of Two Rebamipide Preparations After a Single Oral Dose to Healthy Korean Volunteers

The aims of this study were to evaluate the pharmacokinetic properties and bioequivalence of two rebamipide preparations in healthy Korean male volunteers for generic substitution and to evaluate the association between the genetic polymorphisms in ABCB1 gene (exon 21 and 26) and rebamipide disposition.

Study Overview

• Status: Completed
• Conditions: Pharmacogenetics; Therapeutic Equivalency
• Intervention / Treatment: Drug: Rebamide

Detailed Description

A randomized, single-dose, 2-period crossover design with a 7-day washout period was conducted in 30 healthy Korean male volunteers. Subjects were randomly assigned to receive a single 100-mg dose of the test or reference preparation of rebamipide, administered with 240 mL of water after a 12-hour overnight fast. All subjects were selected after passing a clinical screening procedure that included a physical examination and laboratory tests. Serum concentrations of rebamipide up to 12 hours after administration were determined using a validated HPLC method with fluorescence detection. Adverse events (AEs) were continuously monitored by clinical staff via observation, personal interview, and vital signs (temperature, blood pressure, heart rate) during the study period. All adverse events were recorded on the clinical record form per subject up to 1 week after the study. Pharmacokinetic parameters were determined using a noncompartmental method. The preparations were considered bioequivalent if the log-transformed ratios of AUC0-t, AUC0-∞, and Cmax were within the predetermined bioequivalence range (ie, 80-125%), as set by the US Food and Drug Administration (FDA) and Korean legislation. In vitro dissolution profiles of both preparations were examined and the influence of genetic polymorphisms in ABCB1 gene (P-glycoprotein) on the pharmacokinetics of rebamipide was also investigated.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gwangju, Korea, Republic of, 500-757
    • Institute of Bioeqivalence and Bridging Study, College of Pharmacy, CNU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Subjects were selected after passing a clinical screening procedure that included a physical examination and laboratory tests (blood analysis; hemoglobin, hematocrit, RBC, WBC, platelet, differential counting of WBC, total proteins, albumin, ALT, AST, alkaline phosphatase, total bilirubin, cholesterol, creatinine, blood urea nitrogen, and fasting glucose and urine analysis; specific gravity, color, pH, sugar, albumin, bilirubin, RBC, WBC and cast).

Exclusion Criteria:

• Subjects possibly sensitive to this type of preparation,
• Subjects who had a history of any hepatic illness,
• Subjects who had a history of any renal illness,
• Subjects who had a history of any respiratory illness,
• Subjects who had a history of any endocrine illness,
• Subjects who had a history of any cardiovascular system illness,
• Subjects who had taken alcohol within 4 weeks prior to the study,
• Subjects who had taken other preparations within 4 weeks prior to the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rebamipide, Serum concentration, Tablet; The test preparation, Rebamide® (containing 100 mg of rebamipide; lot No. KP005; expiration date, April 2010; Kyungdong Pharmaceutical Company, Seoul, Korea) and the reference preparation, Mucosta® (containing 100 mg of rebamipide; lot No. MC704067; expiration date, May 2010; Korea Otsuka Pharmaceuticals Co., Ltd., Seoul, Korea)	Drug: Rebamide; Rebamipide 100 mg Tablet, three times a day; Other Names: Mucosta® (Korea Otsuka Pharmaceuticals Co.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Serum concentration of rebamipide	Pre-dose (to serve as a control) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 12 hours after oral administration of rebamipide tablet (100 mg)

Secondary Outcome Measures

Outcome Measure	Time Frame
Genetic polymorphisms in ABCB1 gene (exon 21 and 26)	A 3-mL blood sample was taken from each subject who participated in our bioequivalence studies before administration of rebamipide.

Collaborators and Investigators

• Sponsor: Chonnam National University Hospital
• Collaborators: Institute of Bioequivalence and Bridging Study, College of Pharmacy, CNU
• Investigators: Principal Investigator: Yong-Bok Lee, Ph.D., Institute of Bioequivalence and Bridging Study, College of Pharmacy, CNU

Publications and helpful links

General Publications

• Cho HY, Yoon H, Park GK, Lee YB. Pharmacokinetics and bioequivalence of two formulations of rebamipide 100-mg tablets: a randomized, single-dose, two-period, two-sequence crossover study in healthy Korean male volunteers. Clin Ther. 2009 Nov;31(11):2712-21. doi: 10.1016/j.clinthera.2009.11.010.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: October 14, 2009
• First Submitted That Met QC Criteria: October 18, 2009
• First Posted (Estimate): October 19, 2009

Study Record Updates

• Last Update Posted (Estimate): October 19, 2009
• Last Update Submitted That Met QC Criteria: October 18, 2009
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: Bioequivalence; Rebamipide; ABCB1 genetic polymorphisms
• Other Study ID Numbers: IBBS-BE-REBAMIPIDE-KYUNGDONG