Calcium antagonists in heart transplant recipients: effects on cardiac and renal function and cyclosporine pharmacokinetics.
OBJECTIVE
Cyclosporine increases transmembrane calcium flux in mesangial and vascular smooth muscle cells, which may explain cyclosporine-induced decreases in renal bloodflow and glomerular filtration rate. Calcium antagonists, thus, may play a role in the prevention/reversal of cyclosporine nephrotoxicity.


METHODS
In a single-blind, randomized, cross-over study the authors evaluated the effects of a one-week treatment with nifedipine 20 mg bid, diltiazem 120 mg bid or placebo on cardiac and renal functions of six stable heart transplant recipients treated chronically with cyclosporine.


RESULTS
Both calcium antagonists lowered blood pressure compared with placebo, but only nifedipine increased cardiac output and, therefore, decreased total peripheral resistance significantly more than diltiazem. Nifedipine induced a significant increase in effective renal plasma flow and an insignificant increase in glomerular filtration rate, whereas diltiazem caused a reduction in these parameters. Cyclosporine pharmacokinetics were not affected by either calcium antagonist to a clinically significant extent.


CONCLUSIONS
Nifedipine and diltiazem exert distinctly different cardiac and renal hemodynamic effects in cardiac transplants, which may have clinical consequences.
Legault
L
L
Department of Medicine, Toronto Western Hospital, Ontario.
Ogilvie
R I
RI
Cardella
C J
CJ
Leenen
F H
FH
D016572:Cyclosporine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004110:Diltiazem / Q000627:therapeutic use*; D016027:Heart Transplantation; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007165:Immunosuppression Therapy; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000627:therapeutic use*
D016572:Cyclosporine; D004110:Diltiazem; D009543:Nifedipine