A pharmacokinetic comparison of the corn oil versus microemulsion gelcap formulation of cyclosporin used de novo after renal transplantation.
The initial poor absorption of the corn oil-based, gel capsule oral formulation of cyclosporin (CyA) greatly limits its use for inception of immunosuppressive therapy. Insufficient drug concentrations during the early post-transplant period predispose to renal allograft rejection. The present study served to compare the time required to achieve the therapeutic CyA concentrations after de novo administration of the corn oil-based gel capsule (CyA-GC; n = 11) versus the microemulsion (CyA-ME; n = 11) formulation of CyA. During the 1st month after renal transplantation, patients underwent serial pharmacokinetic profiling from which we obtained observed and dose-corrected values of several parameters. Although patients in neither the CyA-GC nor the CyA-ME group adequately absorbed the drug during days 0-2, from day 3 to 4 patients in the CyA-ME group showed significantly greater absorption than those in the CyA-GC group (P = 0.041). Patients in the CyA-ME group reached the 1st month target average concentration (Cav) values (> or = 550 ng/ml) earlier than those in the CyA-GC group and required significantly lower daily CyA doses (P = 0.018). We conclude that therapeutic CyA levels can be achieved more rapidly and with lower doses of the drug after de novo administration of CyA-ME than with CyA-GC.
Amante
A J
AJ
Department of Surgery, University of Texas Medical School at Houston 77030, USA.
Meier-Kriesche
H U
HU
Schoenberg
L
L
Kahan
B D
BD
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002214:Capsules; D003314:Corn Oil; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004655:Emulsions; D005260:Female; D005782:Gels; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D013997:Time Factors
D002214:Capsules; D004655:Emulsions; D005782:Gels; D007166:Immunosuppressive Agents; D003314:Corn Oil; D016572:Cyclosporine