Evaluation of the pharmacokinetic interaction between fluvastatin XL and cyclosporine in renal transplant recipients.
OBJECTIVE
To assess the pharmacokinetic interaction between cyclosporine and extended-release fluvastatin (fluvastatin XL), 80 mg for 7 days, in stable renal transplant recipients.


METHODS
This was a single-center, open-label study. 17 renal transplant recipients received their standard cyclosporine therapy (Days 1 - 9) plus a once-daily single oral dose of fluvastatin XL, 80 mg (Days 2 - 8). Blood samples were collected and cyclosporine (whole blood) and fluvastatin (plasma) concentrations determined by radioimmunoassay and HPLC fluorescence detection, respectively. Pharmacokinetic parameters were calculated using non-compartment analysis and fluvastatin results were compared with historical controls.


RESULTS
Treatment with fluvastatin XL, 80 mg for 7 days, had no significant effect on either the AUC0-12 (3,644 ng x h/ml in the absence of fluvastatin vs. 3,534 ng x h/ml in the presence of fluvastatin) or the Cmax of cyclosporine (983 ng/ml in the absence of fluvastatin vs. 945 ng/ml in the presence of fluvastatin). Co-administration of fluvastatin XL also had no effect on the tmax, t1/2 or apparent clearance (CL/F) of cyclosporine in renal transplant patients. The AUC and Cmax for fluvastatin XL in the presence of cyclosporine (AUC0-24 1,192 ng. x h/ml, Cmax 271 ng/ml) were approximately 2-fold higher compared with historical data for fluvastatin XL alone in healthy volunteers (AUC0-24 630 ng x h/ml, Cmax 102 ng/ml) but lower than the historical data for fluvastatin IR, 40 mg b.i.d. alone in healthy volunteers (AUC0-24 1,340 ng x h/ml, Cmax 443 ng/ml). Tmax, t1/2 and trough levels of fluvastatin in the presence of cyclosporine were also similar to the historical controls. Concomitant administration of cyclosporine and fluvastatin XL was well tolerated by renal transplant recipients.


CONCLUSIONS
Fluvastatin XL, 80 mg, and cyclosporine do not show clinically relevant pharmacokinetic interactions.
Holdaas
H
H
Department of Medicine, National Hospital, Sognsvannsveien 20, 0027 Oslo, Norway. hallvard.holdaas@rikshospitalet.no
Hagen
E
E
Asberg
A
A
Lund
K
K
Hartman
A
A
Vaidyanathan
S
S
Prasad
P
P
He
Y L
YL
Yeh
C M
CM
Bigler
H
H
Rouilly
M
M
Denouel
J
J
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018501:Antirheumatic Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged
D000924:Anticholesteremic Agents; D018501:Antirheumatic Agents; D003692:Delayed-Action Preparations; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D000077340:Fluvastatin; D016572:Cyclosporine