Conversion from tacrolimus to cyclosporine in stable renal transplant patients: safety, metabolic changes, and pharmacokinetic comparison.
BACKGROUND
Although conversion between tacrolimus and cyclosporine has been performed when indicated for rejection or adverse effects, the safety and metabolic outcome of elective conversion from tacrolimus to cyclosporine has not previously been examined.


METHODS
Conversion from tacrolimus to cyclosporine was performed in 19 recipients of cadaver renal transplants at 3-6 months after transplantation. Pharmacokinetic profiles and biochemical studies were performed three times, in steady state, before, and after conversion.


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/L (P=0.037), and the mean plasma cholesterol rose from 5.2 (3.4-6.8) to 5.5 (3.8-7.6) mmol/L (P=0.033). Pharmacokinetic profiles were measured before and after conversion, and showed that cyclosporine (Neoral) exhibited significantly less interpatient and intrapatient variability than tacrolimus, for area under the curve (AUC), maximum concentration after dose (Cmax), minimum concentration after dose (Cmin), and time to maximum concentration (Tmax).


CONCLUSIONS
This is the first study that has examined the outcome of conversion from tacrolimus- to cyclosporine-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 that cyclosporine in the form of Neoral exhibited less inter- and intrapatient variability than tacrolimus, although this is of uncertain clinical significance.
Higgins
R M
RM
Renal Transplant Unit, Walsgrave Hospital NHS Trust, Coventry, United Kingdom.
Hart
P
P
Lam
F T
FT
Kashi
H
H
D000328:Adult; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D016572:Cyclosporine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000139:chemically induced; D016030:Kidney Transplantation; D008875:Middle Aged; D019233:Retreatment; D016019:Survival Analysis; D016559:Tacrolimus / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D002784:Cholesterol; D016559:Tacrolimus