Cyclosporine safety and bioavailability with two second-generation softgel capsules using serum concentrations/TDM and modeling in transplant patients--a retrospective, parallel, comparative evaluation study.
OBJECTIVE
Deximune soft-gelatin capsules (Dexcel Ltd., Hadera, Israel), the test preparation and Sandimmun Neoral (Novartis Inc., Basel, Switzerland), the reference preparation, are two cyclosporine (CyA) formulations widely used after stem cells and solid organ transplantation. A post-marketing, retrospective, parallel, comparative, multicenter survey study in transplant patients receiving these two formulations after transplantation was carried out in order to compare the toxicity profile and bioavailability.


METHODS
The study was conducted in the five main leading transplantation centers in Israel and included 174 patients. A total of 1-3 CyA serum levels at different periods after transplantation were measured in each subject and the bioavailability, efficacy and toxicity profile were assessed. The blood concentrations were compared using a statistical model after adjustment for type of transplantation, dose and time after transplantation as confounding factors.


RESULTS
No distinct differences were observed between the two CyA formulations. Using model-derived least squares means (LSM) of the CyA blood levels and adjusting for relevant confounding factors, no significant difference could be found between the blood levels of the test and reference formulations. Most of the side effects were mild and transient with both formulations, whereas 23% of the patients reported serious adverse events (mainly hypertension, 15%). 20% of the patients developed infectious complications during the therapy.


CONCLUSIONS
Deximune administration is safe. The toxicity profile of the product, incidence and type of side effects and bioavailability are similar to those of Sandimmun Neoral.
Berger
R
R
Institute of Oncology and Radiotherapy, Sheba Medical Center, Tel Hashomer, Israel.
Avramoff
A
A
Leiba
M
M
Domb
A J
AJ
Laor
A
A
Nagler
A
A
D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D002214:Capsules; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D016903:Drug Monitoring; D005260:Female; D005780:Gelatin; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D007223:Infant; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D012189:Retrospective Studies; D033581:Stem Cell Transplantation
D002214:Capsules; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D005780:Gelatin