The use of Healthy Volunteers to Evaluate Bioequivalence of Antineoplasic Drugs: Pilot Studies with Capecitabine
- *Corresponding Author:
- Gilberto De Nucci
415 Jesuino Marcondes Machado Ave.
13092-320, Campinas - SP, Brazil
E-mail: [email protected]
Received Date: September 05, 2011; Accepted Date: September 30, 2011; Published Date: October 03, 2011
Citation: Mendes GD, Babadopulos T, Chen LS, Ilha JO, de Almeida Magalhães JC, et al. (2011) The use of Healthy Volunteers to Evaluate Bioequivalence of Anti-neoplasic Drugs: Pilot Studies with Capecitabine. J Bioequiv Availab S1: 005. doi: 10.4172/jbb.S1-005
Copyright: © 2011 Mendes GD, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Capecitabine is a prodrug, is selectively activated by tumor cells to its cytotoxic moiety, 5-fluorouracil, by thymidine phosphorylase, which is generally expressed at high levels in tumors. Clinical and pharmacokinetics studies for capecitabine are perfomed in patients with cancer. The objective of the study was to evaluate the safety of a bioequivalence study (150 mg tablet) using healthy male volunteers under fasting and non-fasting conditions. The study was conducted with an open, randomized, two-period crossover design in a 2-week washout interval without food. After the study without food was completed, a new protocol was submitted to the Ethics Committee to evaluate the study with food. The volunteers were selected for the study after having their health status previously assessed by a clinical evaluation and laboratory tests (biochemical and hematological parameters, and urinalysis). A single capecitabine tablet (150mg) was given in each interment. An extra laboratory analysis was performed one week after the first administration of the drug for the safety of the subjects. Plasma capecitabine concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (HPLC/MS/MS) with positive ion electrospray ionization using multiple reactions monitoring (MRM). The pharmacokinetic parameters were 529.38 (±265.22) and 462.88 (±425.85) ng.mL -1 for C max , 262.31 (±75.34) and 300.49 (±91.51) ng.hr.mL -1 for AUC last , and 0.66 (range 0.5 – 1.25) hr and 1.0 (range 0.33 – 1.33) hr for T max , without and with food, respectively, for the reference formulation. The intra-subject CV were 42.6% and 76.3% for C max and 9.64% and 20.3% for AUC last without and with food, respectively. The drug was well tolerated by the volunteers, and they presented no adverse reactions. The biochemical and hematological parameters presented no clinically relevant alterations. Our results indicate that it is safe to perform capecitabine bioequivalence studies in healthy male volunteers.