Pharmacokinetic interaction between cyclosporine and the dihydropyridine calcium antagonist felodipine.
OBJECTIVE
In a double blind, randomised, placebo-controlled, cross-over study 12 healthy male volunteers were allocated to receive felodipine + placebo, cyclosporine + placebo, and felodipine + cyclosporine in order to investigate the interaction between the calcium channel blocker felodipine and cyclosporine as it affects the pharmacokinetics of felodipine, dehydrofelodipine, and cyclosporine, and 24-hour blood pressure measurements.


METHODS
Single doses of cyclosporine (capsules, 5 mg/kg body weight) and of felodipine (extended release (ER) tablets 10 mg) were given at a 1-2 week interval. Plasma drug concentrations were followed for 2 days after drug intake.


RESULTS
For cyclosporine, Cmax was increased after combined treatment (16%) compared to cyclosporine alone, but felodipine did not influence other kinetic parameters of cyclosporine. For felodipine, combined treatment with cyclosporine and felodipine increased AUC and Cmax (58% and 151%, respectively) and lowered mean residence time (24%) significantly compared to felodipine alone. For the metabolite dehydrofelodipine, too, AUC and Cmax were increased after the combined treatment (43% and 94%, respectively). Mean 24-hour systolic and diastolic blood pressures were significantly lower after felodipine, both when felodipine was given alone (121/68 mmHg) and in combination with cyclosporine (122/68 mmHg) compared to cyclosporine alone (127/73 mmHg).


CONCLUSIONS
A combined single dose of cyclosporine and felodipine in healthy subjects increased the AUC and Cmax of felodipine suggesting a cyclosporine-induced decrease in the first-pass metabolism of felodipine, whereas the AUC of cyclosporine was only slightly increased by felodipine.
Madsen
J K
JK
Research Laboratory for Nephrology and Hypertension, Aarhus University Hospital, Denmark.
Jensen
J D
JD
Jensen
L W
LW
Pedersen
E B
EB
D000328:Adult; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004347:Drug Interactions; D015736:Felodipine / Q000493:pharmacokinetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D008297:Male
D002121:Calcium Channel Blockers; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D015736:Felodipine