Comparative bioavailability study of capecitabine tablets of 500 mg in metastatic breast cancer and colorectal cancer patients under fed condition

Pharmacokinetics and pharmacogenetics of capecitabine and its metabolites following replicate administration of two 500 mg tablet formulations

“…The pharmacokinetic properties of the two formulations are in accordance with reported literature data. The mean capecitabine dose in this study was 1739 mg; compared to other bioequivalence studies that investigated doses of 2000 mg, similar values for AUC, T max , C max and t½ λ z were observed [6,20,21]. Pharmacokinetics of capecitabine for a higher dose (1.75 g/m 2 ) as compared to the standard dose (1.25 g/m 2 ) did not provide evidence for a saturation of pharmacokinetic processes or any significant delay of elimination [22]; thus, the differing (patient-specific) doses administered in this study were not expected to have a major impact on pharmacokinetic variability.…”

“…This, however, is not an acceptable procedure according to actual guidelines [10]. Two more recent studies conducted in India were able to show bioequivalence for capecitabine preparations comparing 500 mg tablet formulations [20,21]. Both studies were designed as two-period, two-sequence crossover studies with a single administration of a fixed dose (four tablets/2000 mg) of test and reference formulation.…”

“…Both studies were designed as two-period, two-sequence crossover studies with a single administration of a fixed dose (four tablets/2000 mg) of test and reference formulation. With an estimated sample size of 88 and accounting for a 20 % dropout rate, Gadiko et al [20] included 110 patients, of which five did not complete the study and two had relevant pre-dose capecitabine concentrations, and thus 103 patients could be evaluated. In the study of Chachad et al [21], 63 of 73 recruited patients were considered for the final pharmacokinetic assessment, while neither the estimation of sample size nor the criteria for exclusion from analysis are described.…”

“…In the study of Chachad et al [21], 63 of 73 recruited patients were considered for the final pharmacokinetic assessment, while neither the estimation of sample size nor the criteria for exclusion from analysis are described. Reported within-subject CV values for C max (calculated from remaining variability in the absence of a replicate design) were 39.6 % [20] and 50.4 % (back-calculated from CIs) [21]. Thus, while clinical and analytical performance as well as the study design for the present study provided a low within-subject variability of C max (CV 30.2 %), the lower T/R ratio for C max of 0.872 as compared to the published data (0.920 [20] and 0.9351 [21]) was the reason for missing bioequivalence.…”

A conserved enzyme found in diverse human gut bacteria interferes with anticancer drug efficacy

“…1a ). CAP meets the FDA criteria for a “highly variable” drug, with a coefficient of variation >30% in intra-subject pharmacokinetic parameters combined with extensive variation between subjects 11 that cannot be explained by the known host risk factors 12,13 . Adverse reactions to CAP require dose adjustments in ∼35% of patients and complete discontinuation of therapy in ∼10% of patients; GI side effects are common 14,15 .…”