[Evaluation of the bioequivalence of two fast-releasing iron(II) sulfate formulations]

Bioequivalence of a new oral iron formulation (A: FE(II)SO4.H2O, capsule with 100 mg Fe++, Eryfer 100, CAS 7782-63-0) with the standard formulation (B: Fe(II)SO4.H2O, capsule with 50 mg Fe++, Eryfer) was demonstrated after administration of 100 mg Fe++ in a single-dose two-way cross-over design to 16 normal female volunteers. Iron concentrations were monitored from 24 h before (basal) to 24 h post application. The area under concentration difference curve AUC(diff) and the maximal concentration difference Cmax(diff) were calculated subtracting the basal from the time-corresponding postabsorptive concentrations. AUC(diff) (A: 170 nmol/ml. h, B: 168 nmol/ml.h) and Cmax(diff) (A: 23.3 nmol/ml, B: 21.8 nmol/ml) showed but minor differences between formulations. The AUC(diff) and Cmax ratio (A/B) and the corresponding 90% confidence intervals, 102% (74-129%) and 107% (91-123%), were included by the acceptance range of 70-130% as stated in the study protocol. Hence, both formulations were bioequivalent with respect to rate and extent. The ANOVA coefficient of variation of Cmax(diff) was considerably smaller than that of AUC(diff) (26% versus 44%). The characteristics based on the postabsorptive iron increase (post-absorptive concentrations minus concentration preceding immediately application) AUC(pad) (ratio 99% (83-114%) and Cmax(pad) (ratio 104% (95-112%) exhibited smaller ANOVA-CVs (25% and 14%, respectively) as compared with AUC(diff) and Cmax(diff). All these characteristics appeared to be rather normal than log-normal distributed. It was concluded that the study design was selective to demonstrate an adequate bioavailability of iron formulations.