61279
document
Novel population pharmacokinetic method compared to the standard noncompartmental approach to assess bioequivalence of iron gluconate formulations . PURPOSE Iron-containing products are atypical in terms of their pharmacokinetic properties because iron is only removed by plasma sampling and is non-linear . This study aims to present a novel way of assessing the relative bioavailability of two sodium ferric gluconate complex ( SFGC ) formulations and compare this approach to a standard previously published noncompartmental approach . METHODS Data were from open-label , randomized , single-dose studies ( Study 1 was parallel whereas Study 2 was crossover ) . Subjects with low but normal iron levels were infused IV SFGC in sucrose by GeneraMedix Inc. and/or Ferrlecit ® Injection ( Watson Laboratories Inc. ) . In Study 1 ( n=240 ) , 125 mg was infused over 10 minutes . In Study 2 ( n=29 ) , 62.5 mg was infused over 30 minutes . Samples were assayed for total iron ( TI ) and transferrin-bound iron ( TBI ) over 36 hours ( Study 1 ) or 72 hours ( Study 2 ) post-dose . Studies 1 and 2 used standard noncompartmental analysis . Study 2 also used population PK ( PPK ) analyses with ADAPT 5® . The final model predicted SFGC area-under-the-curve ( AUCpred ) and maximal concentration ( Cmaxpred ) . Analyses of variance was conducted on ln-transformed PK parameters . Ratios of means and 90 % confidence intervals ( CIs ) were estimated . Bioequivalence was demonstrated if values were within 80-125 % . RESULTS For Study 1 , ratios and 90 % CIs for TI baseline-corrected Cmax and AUC0-36 were 100.4 ( 96.5 - 104.5 ) and 99.7 ( 94.2 - 105.5 ) . For TBI , results for TI baseline-corrected Cmax and AUC0-36 were 86.8 ( 82.7 - 91.1 ) and 92.4 ( 85.6 - 99.7 ) . For Study 2 , a multi-compartmental model simultaneously described the PK of TI , TBI and SFGC . Ratios and 90 % CIs for SFGC Cmaxpred and AUCpred were 89.9 ( 85.9 - 94.0 ) and 89.7 ( 85.7 - 93.9 ) , while ratios and 90 % CI obtained from the noncompartmental analysis of Study 2 did not meet BE criteria because of low power . CONCLUSIONS Both the standard and PPK modeling approach suggested bioequivalence between the iron products . However , with the PPK method , less subjects were required to meet study objectives compared to the standard noncompartmental approach which required considerably more subjects ( 29 vs 240 ) .
61280
Intervention_Pharmacological
sodium ferric gluconate complex ( SFGC )
61281
Intervention_Pharmacological
IV SFGC in sucrose