Bioavailability of two oral formulations of cyclosporin A in uremic children before renal transplantation
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The bioavailability of two oral formulations of cyclosporin A (Sandimmun and Neoral™) was assessed in 10 children with end-stage renal disease (ESRD), while at a steady state on a dialytic procedure. The study was performed according to a randomized, double blind, cross-over design, allowing a 1-month washout period between studies. Each patient received 2.5 mg/μg of oral cyclosporin A every 12 h, either Sandimmun (SAN) or Neoral (NEO). Serum concentrations of cyclosporin A were determined serially during a 24 h period, after the 5th dose of cylosporin. Serum concentrations against time curves were constructed and bioavailability of both medications, expressed as AUC and C max, were compared. A statistically significant increase was observed in the AUC and C max of NEO, which were 90%25 and 130%25 higher, respectively, than those of SAN. Considering that the internationally accepted criteria for bioequivalence allows a 20%25 variation in AUC and C max, it appears that Neoral and Sandimmun do not bear bioequivalence in children with ESRD. Notwithstanding, there were no significant differences in trough levels between both formulations. We conclude that, if trough levels are the only source of information for dosing design, Neoral could be substituted for Sandimmun on a 1:1 basis. However, a 1:1 drug substitution is not suitable when AUC is used in children with ESRD. © Munksgaard 1998.
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Cyclosporin A; End-stage renal disease; Immunosuppression; Neoral bioavailability; Pharmacokinetics; Sandimmun cyclosporin; immunosuppressive agent; area under the curve; article; bioavailability; chemistry; child; clinical trial; controlled clinical trial; controlled study; crossover procedure; double blind procedure; female; human; kidney transplantation; male; metabolism; oral drug administration; preschool child; randomized controlled trial; uremia; Administration, Oral; Area Under Curve; Biological Availability; Child; Child, Preschool; Cross-Over Studies; Cyclosporine; Double-Blind Method; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Uremia
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