PHARMACOKINETIC EFFECTS OF CONVERSION TO A NEW FORMULATION OF CYCLOSPORINE-A IN RHEUMATOID-ARTHRITIS PATIENTS

In this study we aimed at evaluating the modifications in the pharmaco kinetic profile of cyclosporin A (CyA) after conversion from standard formulation (CyA-ST) to a new formulation (CyA-NF, Sandimmun Neoral) i n patients with rheumatoid arthritis (RA). It was an open, crossover s tudy that involved 15 RA patients who were on stabilized treatment wit h CyA-ST. The patient continued receiving CyA-ST (mean dose of 3.0+/-0 .7 mg/kg per day) for 3 weeks and then converted 1 : 1 to CyA-NF for a further 3 weeks. CyA pharmacokinetics were established on day 1 (CyA- ST evaluation) and +21 (CyA-NF evaluation). The results showed that th e bioavailability of CyA-NF was greater than that of CyA-ST (AUC tau, bss: 3335+/-1300 vs 2667+/-1155 ng . h/ml, P=0.0073; AUC tau, bss rati o 1.26+/-0.40 vs 1.0 as reference, P<0.05), with higher and earlier pe ak blood concentrations (C-max: 677+/-256 vs 475+/-213 ng/ml, P=0.0329 ; t(max): 1.5+/-0.7 vs 2.6+/-1.6 h, P=0.0720). The pharmacokinetic pro file of CyA-NF showed greater between-patient reproducibility (lower C V% for all of the considered parameters). In conclusion, when using Cy A-NF instead of CyA-ST, greater and more constant exposure to CyA shou ld be expected.