Bioequivalence and Bioavailability Forum

Olá Maurício!

20 mg/kg, 4way cross-over, n=28: A (before high-fat breakfast), B (before standard breakfast), C (with breakfast), D (fasting).¹
              Ratio (90% CI)
        AUC0-t             Cmax
A  1.23 (1.13–1.33)   1.25 (1.14–1.37)
B  1.21 (1.12–1.32)   1.19 (1.09–1.31)
C  1.49 (1.37–1.62)   1.47 (1.34–1.61)
     CVintra (%)*
    AUC0-t  Cmax
A    18.5  20.9
B    18.6  20.9
C    19.0  20.9

Open-label, randomized, 4-period, crossover study in 28 healthy male volunteers who received single 20 mg/kg oral doses of deferasirox without dispersion (A), dispersed in orange juice (B), dispersed in apple juice (C), and dispersed in non-carbonated water (D, reference).²
               Ratio (90% CI)
        AUC0-t             Cmax
A  1.01 (0.93–1.10)   0.98 (0.87–1.10)
B  1.03 (0.95–1.12)   1.08 (0.96–1.21)
C  0.90 (0.83–0.98)   0.88 (0.79–0.98)
     CVintra (%)*
    AUC0-t  Cmax
A    19.0  26.8
B    18.7  26.5
C    18.8  24.6

I assumed 4×4 designs. I would expect a common variance and therefore, identical CVs. Maybe the differences are due to limited precision of the reported CIs. Take the CVs with a grain of salt.

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1. FDA’s NDA 21-882, Table 21 (2005)
   
2. Séchaud et al.
   Relative bioavailability of deferasirox tablets administered without dispersion and dispersed in various drinks
   Int J Clin Pharmacol Ther 66/2, 102–8 (2008)

• For the method of calculating CV_intra from the CI see this presentation (slides 26–31).