Conversion from tacrolimus to cyclosporin in stable renal transplant patients: safety, metabolic changes, and pharmacokinetic comparison.
BACKGROUND
Conversion from tacrolimus to cyclosporin has not previously been reported as routine clinical practice, but only as indicated by rejection or adverse effects.


METHODS
The safety and metabolic outcome of elective conversion from tacrolimus to cyclosporin was examined in 19 recipients of cadaver renal transplants. Conversion was performed in stable patients at 3-6 months after transplantation.


RESULTS
Patient and graft survival was 100% at 3 months after conversion, with no rejection episodes. Three patients have been subsequently converted back to tacrolimus, two for rejection and one for hirsutism. There were no significant changes in creatinine, urate, or blood sugar levels after conversion, but the mean plasma magnesium rose from 0.73 (0.63-0.97) to 0.82 (0.65-1) mmol/liter (P=0.037), and the mean plasma cholesterol rose from 5.2 (3.4-6.8) to 5.5 (3.8-7.6) mmol/liter (P=0.033). Pharmacokinetic profiles were measured before and after conversion, and showed that cyclosporin (Neoral) exhibited significantly less interpatient and intrapatient variability than tacrolimus, for area under the curve (AUC), maximum concentration postdose (Cmax), minimum concentration postdose (Cmin), time to maximum concentration (Tmax).


CONCLUSIONS
This is the first study that has examined the outcome of conversion from tacrolimus- to cyclosporin-based immunosuppression in stable patients after renal transplantation. This conversion was performed without early immunological hazard, but there was a small rise in blood cholesterol levels after conversion. Pharmacokinetic studies showed cyclosporin in the form of Neoral showed less inter- and intrapatient variability than tacrolimus, although this is of uncertain clinical significance.
Renal Transplant Unit, Walsgrave Hospital NHS Trust, Coventry, UK.
R M
RM
Higgins
P
P
Hart
F T
FT
Lam
H
H
Kashi
D000328:Adult; D002784:Cholesterol / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016527:Drug Costs; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008875:Middle Aged; D016559:Tacrolimus / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D002784:Cholesterol; D016559:Tacrolimus