Rimonabant affects cyclosporine a, but not tacrolimus pharmacokinetics in renal transplant recipients.
BACKGROUND
Obesity is a common problem following renal transplantation. Rimonabant, a cannabinoid-1 receptor blocker, offers a new approach for reducing obesity.


METHODS
The potential pharmacokinetic interaction between rimonabant and cyclosporine A (CsA, n=10) and tacrolimus (Tac, n=8) was assessed in stable renal transplant recipients 6.2 (0.9-21.7) years posttransplant. A 12-hour pharmacokinetic profile was obtained before and after two months of concomitant treatment with 20 mg rimonabant each morning.


RESULTS
Rimonabant treatment induced a moderate, but significant increase in CsA AUC0-12 (19.8+/-16.1 %, P=0.005). Cmax and C2 values tended to increase whereas C0 remained unaffected. Tac pharmacokinetics was not significantly affected by rimonabant treatment. Eleven of 18 patients experienced adverse events. Two patients reported depressions and one reported severe nightmares.


CONCLUSIONS
The effect on CsA pharmacokinetics is probably of marginal clinical relevance since trough concentrations were unaltered, but CsA concentrations should probably be more closely monitored if rimonabant treatment is initiated, preferably by C2 monitoring.
Amundsen
Rune
R
Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway. rune.amundsen@farmasi.uio.no
Asberg
Anders
A
Robertsen
Ida
I
Vethe
Nils T
NT
Bergan
Stein
S
Hartmann
Anders
A
Midtvedt
Karsten
K
D000328:Adult; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D002102:Cadaver; D002186:Cannabinoids / Q000009:adverse effects*; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D007700:Kinetics; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D000077285:Rimonabant; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014019:Tissue Donors
D019440:Anti-Obesity Agents; D002186:Cannabinoids; D010880:Piperidines; D011720:Pyrazoles; D016572:Cyclosporine; D000077285:Rimonabant; D016559:Tacrolimus