Is cyclosporine in renal-transplant recipients more effective when given twice a day than in a single daily dose?
BACKGROUND
It is still unknown whether it is better to administer cyclosporine (CsA) once or twice a day to renal-transplant patients.


METHODS
Fifty-four patients were randomized to receive CsA once a day (OD group, 28 patients) or twice a day (BD group, 26 patients). Clinical parameters and pharmacokinetic studies were regularly monitored over the first year.


RESULTS
Two patients lost their grafts because of renal vascular thrombosis. A patient in the BD group died. The other 51 patients were alive with graft functioning after a minimum follow-up of 1 year. Five patients per group had reversible acute rejection. There was a not significant trend toward a lower mean serum creatinine in OD than in BD (1.38 +/- 0.38 and 1.7 +/- 0.80 mg/dL at 1 year posttransplant, respectively). In 47 patients, 319 pharmacokinetic studies were performed. We measured the area under the concentration-time curve during the first 4 hours (AUC0-4) and CsA blood levels at 0, 2, and 4 hours after dosing. C0 was significantly lower in OD than in BD (P=0.0011), whereas C2 (P<0.0001) and C4 (P<0.0001) were significantly higher in OD than in BD. In OD, the AUC was higher than in BD (P<0.0001). OD allows us to reach high levels of C2 and AUC for several hours after dosing, whereas BD showed persistently high levels throughout the whole day.


CONCLUSIONS
No difference in survival and rejection rates were observed between OD and BD groups.
Tarantino
Antonio
A
Ospedale Maggiore-IRCCS, U.O. Nefrologia e Dialisi, via della Comenda 15, 20122 Milan, Italy.
Passerini
Patrizia
P
Campise
Mariarosaria
M
Bonizzoni
Erminio
E
Ceccarini
Fulvia
F
Montagnino
Giuseppe
G
Aroldi
Adriana
A
Ponticelli
Claudio
C
D000328:Adult; D019540:Area Under Curve; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004655:Emulsions; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007674:Kidney Diseases / Q000145:classification / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D008875:Middle Aged
D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine