Lack of effect of the calcium antagonist isradipine on cyclosporine pharmacokinetics in renal transplant patients.
Hypertension has emerged as a frequent side effect in transplant recipients on effective doses of cyclosporine (CsA). To control hypertension in renal transplant patients, calcium channel blockers have been used; some of these, however, have been shown to cause significant increases in CsA levels. These findings point out that possible interactions of each calcium antagonist with CsA deserve investigation. We performed an open, placebo-controlled study in 12 stable renal transplant recipients to determine whether short-term isradipine influences CsA pharmacokinetics. All patients had mild to moderate hypertension and received triple immunosuppressive therapy with CsA, azathioprine, and prednisolone. Throughout a 4-week period of isradipine treatment, blood CsA levels (specific and nonspecific monoclonal antibodies) remained stable. The mean trough specific level was 121 +/- 14 micrograms/L following placebo, compared to 120 +/- 14 micrograms/L during isradipine. Corresponding non-specific values were 465 +/- 68 and 474 +/- 63 micrograms/L. Also, values for Cmax, AUC, and t1/2 were not significantly changed following 4 weeks of isradipine. Mean arterial pressure was significantly reduced at the end of the study. This study implies that isradipine does not influence CsA metabolism. Further studies should be carried out to determine its long-term effects on CsA pharmacokinetics and renal function in transplanted patients.
Endresen
L
L
Institute of Clinical Biochemistry, University of Oslo, Norway.
Bergan
S
S
Holdaas
H
H
Pran
T
T
Sinding-Larsen
B
B
Berg
K J
KJ
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology*; D016572:Cyclosporine / Q000009:adverse effects / Q000493:pharmacokinetics*; D004095:Dihydropyridines / Q000009:adverse effects / Q000494:pharmacology*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D017275:Isradipine; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D016572:Cyclosporine; D017275:Isradipine