A bioavailability study of cyclosporine: comparison of Neoral versus Cysporin in stable heart transplant recipients.
BACKGROUND
Cyclosporine in the form of a microemulsion (Neoral) has been the cornerstone of the majority of immunosuppression regimes in thoracic organ transplantation. Cysporin, an alternative form of cyclosporine, is now available. Although bioavailability has been studied in healthy volunteers and stable renal transplant recipients, there are no bioequivalence data currently available for the population of thoracic organ transplant recipients. This randomized, 2-arm, crossover, open-label study compares the pharmacokinetic profiles of two formulations of cyclosporine (Neoral and Cysporin) in stable heart transplant patients.


METHODS
The pharmacokinetics of Neoral and Cysporin were assessed on 2 study days in 16 stable heart transplant recipients already receiving Neoral, who were at least 15 months post-transplant and had not undergone dose adjustments of Neoral for the previous 3 months. Participants were randomized to receive one study drug for at least 2 weeks with crossover to the other arm for a further 2 weeks. Drug levels were measured from blood samples obtained on the study day at the end of each phase at baseline (pre-dose) and 1, 1.5, 2, 2.5, 3, 4, 6 and 8 hours post-dose.


RESULTS
The two formulations of cyclosporine were not found to be bioequivalent for C(max). There was less cyclosporine absorbed with Cysporin than with Neoral (ratio 1.31, 90% confidence intervals 1.20 to 1.42) and, although statistically bioequivalent for area under the curve (AUC), a reduction was observed with the new formulation (ratio 1.17, 90% confidence intervals 1.1 to 1.23). The best fit with AUC was observed at 6 hours post-dose for Neoral and 1.5 hours for Cysporin, not the 2 hours post-dose used clinically.


CONCLUSIONS
This study suggests that Cysporin may not be clinically bioequivalent to Neoral in heart transplant recipients. The clinical implications of this observation require further exploration in a larger patient cohort.
Leet
Angeline
A
Cardiology Department, Alfred Hospital, Melbourne, Victoria, Australia.
Richardson
Meroula
M
Senior
Jodie-Anne
JA
Funston
Robyn
R
Skiba
Marina
M
Bailey
Michael
M
Krum
Henry
H
D000704:Analysis of Variance; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008657:Metabolic Clearance Rate; D009862:Online Systems; D013997:Time Factors
D007166:Immunosuppressive Agents; D016572:Cyclosporine