Pharmacokinetic effects of conversion to a new formulation of cyclosporin A in rheumatoid arthritis patients.
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.
Marchesoni
A
A
Rheumatology Unit, G. Pini Orthopaedic Hospital, Milano, Italy.
Fantini
F
F
Battafarano
N
N
Zeni
S
S
Ruiu
G
G
Padula
A
A
Taglione
E
E
Pasero
G
G
Leoni
L
L
D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003404:Creatinine / Q000097:blood; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003627:Data Interpretation, Statistical; D003971:Diastole; D004305:Dose-Response Relationship, Drug; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D005885:Gingival Hyperplasia / Q000139:chemically induced; D006261:Headache / Q000139:chemically induced; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007596:Joints / Q000187:drug effects / Q000473:pathology; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D013599:Systole; D013997:Time Factors; D014202:Tremor / Q000139:chemically induced; D014527:Uric Acid / Q000378:metabolism
D006454:Hemoglobins; D007166:Immunosuppressive Agents; D014527:Uric Acid; D016572:Cyclosporine; D003404:Creatinine