Effect of calcium-channel blockers on cyclosporine clearance and use in renal transplant patients.
OBJECTIVE
To determine the effect of calcium-channel blockers (CCBs) on cyclosporine dose, clearance, and cost, and their effect on kidney graft function and survival in patients who underwent kidney transplant.


METHODS
A total of 176 adults receiving 177 transplants were studied retrospectively. Patients were stratified as follows: no CCB (n = 57), diltiazem (n = 13), nifedipine (n = 37), and verapamil (n = 70). Patients received cyclosporine 3-4 mg/kg by continuous infusion for 5 days followed by cyclosporine 10 mg/kg/d po to maintain initial whole blood concentrations of 300-400 ng/mL. Clearance of intravenously administered cyclosporine was calculated following at least 48 hours of the same dose by continuous infusion. The amount and cost of cyclosporine used during the first 10 days of oral therapy were also calculated.


RESULTS
Patients receiving diltiazem, but not verapamil or nifedipine, had decreased clearance of intravenously administered cyclosporine compared with that of the mean control group. The mean clearance of intravenously administered cyclosporine +/- SD in patients receiving no CCB was 5.1 +/- 1.5 mL/min/kg, diltiazem was 3.7 +/- 0.8 mL/min/kg, nifedipine was 6.4 +/- 1.9 mL/min/kg, and verapamil was 5.2 +/- 2.2 mL/min/kg. The amount and cost of 10 days of oral cyclosporine therapy was decreased in the verapamil group (5.7 +/- 1.5 g and $257 +/- 69) compared with that of the control group (6.7 +/- 1.6 g and $304 +/- 72) (p < 0.001). There was no significant difference among the groups with respect to immediate graft function, 1-year serum creatinine concentration, or 1-year graft survival.


CONCLUSIONS
Diltiazem decreased the clearance of intravenously administered cyclosporine. Although verapamil did not decrease the clearance of intravenously administered cyclosporine, it allowed a significant reduction in oral cyclosporine cost without apparent adverse effects on graft function. Further work is needed to determine the effect of CCBs on cyclosporine pharmacokinetics, especially with respect to their metabolism by gut and hepatic cytochrome P-450 enzymes, and their effect on patient outcome.
Sketris
I S
IS
College of Pharmacy, Dalhousie University, Halifax, Nova Scotia.
Methot
M E
ME
Nicol
D
D
Belitsky
P
P
Knox
M G
MG
D000284:Administration, Oral; D000328:Adult; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D016572:Cyclosporine / Q000008:administration & dosage / Q000191:economics / Q000493:pharmacokinetics*; D004110:Diltiazem / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006085:Graft Survival; D006801:Humans; D007165:Immunosuppression Therapy; D007262:Infusions, Intravenous; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000494:pharmacology; D009674:Nova Scotia; D012189:Retrospective Studies; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D016572:Cyclosporine; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine