title: Comparison of pharmacokinetics and safety profiles of two capecitabine tablet formulations in patients with colon, colorectal or breast cancer.
abstract: OBJECTIVE
  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 C(max), AUC(0-t) and AUC(0-∞) 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 C(max), AUC(0-t) and AUC(0-∞) 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.
authors.affiliation: Department of Clinical and Bioequivalence Research, Cipla Limited, 3rd Floor C Wing, Raj Plaza, LBS Marg, Vikhroli, 400083 Mumbai, India. siddharth.chachad@cipla.com
authors.forename: Siddharth
authors.initials: S
authors.lastname: Chachad
authors.forename: Shrinivas
authors.initials: S
authors.lastname: Purandare
authors.forename: Geena
authors.initials: G
authors.lastname: Malhotra
authors.forename: Raghu
authors.initials: R
authors.lastname: Naidu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000188:drug therapy*; D000069287:Capecitabine; D003110:Colonic Neoplasms / Q000188:drug therapy*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018592:Cross-Over Studies; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D000964:Antimetabolites, Antineoplastic; D013607:Tablets; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil