Bioequivalence of Two Formulations (Innovator vs Generic) of Capecitabine in Patients with Cancer of Colon

Ruiz-García Erika Betzabe

doi:10.11648/j.crj.20150306.11

Abstract

Capecitabine is an orally administered chemotherapeutic agent used in the treatment of numerous cancers including colon, colorectal, ovarian, breast and pancreatic. Considering the importance of generic drugs in Health Care Systems, it is essential that its quality, safety and efficacy be compared with the corresponding innovator product. The objective of the study was to compare the pharmacokinetics and relative bioequivalence between two tablet (500 mg) formulations of capecitabine in Mexican patients with cancer of colon. The study was designed as open, prospective, randomized, two-way, crossover bioequivalence trial. A single oral dose of 2000 mg capecitabine was administered on two separate days to 24 patients. After each administration, serial blood samples were collected for up 8 hr. The washout between the two administrations was 3 days. Capecitabine was determined in plasma using LC/MS-MS. No statistically significant differences in Cmax, AUC0-t, and AUC0-α were found between the test and innovator formulations. Both products were well tolerated by the patients, with no serious adverse events. The generic capecitabine was pharmacokinetic bioequivalent with the innovator formulations.

Highlights

Capecitabine a fluoropyrimidene carbamate rationally designed as orally administered is currently approved by the FDA (Food and Drug Administration) EMA (European Medicinal Agency) and COFEPRIS (Federal Commission against Sanitary Risks, Mexico) as adjuvant in patients with colon, colorectal [1,2,3], breast [4, 5], ovarian [6, 7] and pancreatic [8,9,10] cancer, in combination with other antineoplasic drugs
Capecitabine a prodrug is selectively activated by tumor cells to its cytotoxic moiety, 5-fluorouracil (5-FU), by thymidine phosphorylase, which is generally expressed at high levels in tumors [11, 12]
The aim of this study was to evaluate the pharmacokinetic of two-capecitabine tablets formulation, innovator versus generic in patients with colon cancer

Summary

Introduction

Capecitabine a fluoropyrimidene carbamate rationally designed as orally administered is currently approved by the FDA (Food and Drug Administration) EMA (European Medicinal Agency) and COFEPRIS (Federal Commission against Sanitary Risks, Mexico) as adjuvant in patients with colon, colorectal [1,2,3], breast [4, 5], ovarian [6, 7] and pancreatic [8,9,10] cancer, in combination with other antineoplasic drugs. Capecitabine a prodrug is selectively activated by tumor cells to its cytotoxic moiety, 5-fluorouracil (5-FU), by thymidine phosphorylase, which is generally expressed at high levels in tumors [11, 12]. Capecitabine and its intermediate metabolites, 5-Deoxy-5-Fluorouracil (5-DFUR) are not intrinsically cytotoxic. The intermediate 5-DFUR is converted to 5-FU by the enzyme thymidine phosphorylase, which has significantly higher activity in tumor than the normal tissue [13,14,15,16]. Capecitabine has almost 100% oral bioavailability and exhibits linear increases in maximum plasma concentration (Cmax) and area under curve (AUC) with dosage increases [13]. In comparison Cmax for the active metabolite, 5-FU is lower at 0.66 mg/L with similar time to reach maximum concentration (Tmax) of 2 hours.

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