Rheumatol Int

Pharmacokinetic effects of conversion to a new formulation of cyclosporin A in rheumatoid arthritis patients.

Year 1998
Marchesoni A. Fantini F. Battafarano N. Zeni S. Ruiu G. Padula A. Taglione E. Pasero G. Leoni L.
Rheumatology Unit, G. Pini Orthopaedic Hospital, Milano, Italy.
In this study we aimed at evaluating the modifications in the pharmacokinetic profile of cyclosporin A (CyA) after conversion from standard formulation (CyA-ST) to a new formulation (CyA-NF, Sandimmun Neoral) in patients with rheumatoid arthritis (RA). It was an open, crossover study that involved 15 RA patients who were on stabilized treatment with 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 the 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 ratio 1.26 +/- 0.40 vs 1.0 as reference, P < 0.05), with higher and earlier peak blood concentrations (Cmax: 677 +/- 256 vs 475 +/- 213 ng/ml, P = 0.0329; tmax: 1.5 +/- 0.7 vs 2.6 +/- 1.6 h, P = 0.0720). The pharmacokinetic profile of CyA-NF showed greater between-patient reproducibility (lower CV% for all of the considered parameters). In conclusion, when using CyA-NF instead of CyA-ST, greater and more constant exposure to CyA should be expected.