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Comparison of pharmacokinetics and safety profiles of two capecitabine tablet formulations in patients with colon, colorectal or breast cancer

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Abstract

Purpose

The objective of this study was to compare the pharmacokinetics and safety of two tablet formulations containing 500 mg of capecitabine (CAS number 154361-50-9) in patients with colon, colorectal or breast cancer.

Methods

The study was a multicentric, open label, randomized, two-treatment, two-period, two-sequence, single dose, crossover bioequivalence study in patients of either sex with colon, colorectal or breast cancer. Eligible patients received each treatment in a crossover manner under fed conditions according to the randomization schedule. The pre-dose blood sample was taken within 90 min prior to dosing, and serial blood sampling was done up to 10.00 h post-dose under monochromatic light. The analysis of plasma samples for concentrations of capecitabine and 5′-deoxy-5-fluorocytidine (5′-DFCR) was carried out using a validated liquid chromatography mass spectrometry method. Bioequivalence was to be concluded if the confidence intervals so constructed were within the range of 80–125 % for Cmax, AUC0−t and AUC0−∞ of capecitabine and 5′-DFCR. Patients were monitored for safety and tolerability throughout the study.

Results

The 90 % confidence intervals for the “test/reference” mean ratios of the ln-transformed pharmacokinetic variables Cmax, AUC0−t and AUC0−∞ were clearly within the conventional bioequivalence range of 80–125 %. Both the formulations were reasonably tolerated after a single oral dose in patients.

Conclusions

Both the capecitabine tablet formulations demonstrated equivalent rate and extent of systemic absorption, and hence were considered bioequivalent. Therefore, the two formulations can be considered as equivalent in terms of pharmacokinetics and safety profiles.

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Acknowledgments

This study was sponsored by Cipla Limited, India.

Conflict of interest

No author of this proposed publication has financial disclosure or conflict interest in the subject matter discussed in this manuscript.

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Authors and Affiliations

  1. Department of Clinical and Bioequivalence Research, Cipla Limited, 3rd Floor C Wing, Raj Plaza, L. B. S. Marg, Vikhroli (W), 400083, Mumbai, India

    Siddharth Chachad, Shrinivas Purandare & Geena Malhotra

  2. Contract Research Organisation, Sitec Labs Pvt Ltd, Mumbai, India

    Raghu Naidu

Authors
  1. Siddharth Chachad
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  2. Shrinivas Purandare
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  3. Geena Malhotra
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  4. Raghu Naidu
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Correspondence to Siddharth Chachad.

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Chachad, S., Purandare, S., Malhotra, G. et al. Comparison of pharmacokinetics and safety profiles of two capecitabine tablet formulations in patients with colon, colorectal or breast cancer. Cancer Chemother Pharmacol 71, 287–292 (2013). https://doi.org/10.1007/s00280-012-2007-7

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  • DOI: https://doi.org/10.1007/s00280-012-2007-7

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