Pharmacokinetics of cyclosporine in hyperlipidaemic long-term survivors of heart transplantation. Lack of interaction with the lipid-lowering agent, fenofibrate.
Cyclosporine (Cy) binds to lipoproteins in plasma. In order to test if its pharmacokinetics would be modified when efficient lipid-lowering treatment is introduced, a study has been done of Cy pharmacokinetics and any interaction with the lipid-lowering agent fenofibrate in hyperlipidaemic long-term, survivors of heart transplantation. Fenofibrate 200 mg once daily significantly reduced blood lipids (cholesterol 6.5 vs 7.7 mmol/l; apoprotein B 1.2 vs 1.6 g/l) but did not modify mean whole blood Cy trough levels (113 before fenofibrate vs 103 ng.ml-1), Cmax (812 ng.ml-1 by RIA and 757 ng.ml-1 by HPLC before fenofibrate versus 865 and 741 respectively, during fenofibrate); tmax (1.6 and 1.7 h before fenofibrate versus 1.4 and 1.4 h respectively), and t1/2 (13.9 and 11.1 h versus 9.5 and 10.7 h). The only adverse effect was an increase in creatinine (157 vs 145 mmol/l). Further studies are needed to investigate the mechanism of Cy-fenofibrate nephrotoxicity and to evaluate the long-term efficiency and safety of fenofibrate after heart transplantation.
deLorgeril
M
M
INSERM, U 63, Daix, France.
Boissonnat
P
P
Bizollon
C A
CA
Guidollet
J
J
Faucon
G
G
Guichard
J P
JP
Levy-Prades-Sauron
R
R
Renaud
S
S
Dureau
G
G
D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D011345:Fenofibrate / Q000494:pharmacology*; D016027:Heart Transplantation / Q000401:mortality; D006801:Humans; D006949:Hyperlipidemias / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D013997:Time Factors
D016572:Cyclosporine; D011345:Fenofibrate