Safety, tolerability, and pharmacokinetic actions of diltiazem in pediatric liver transplant recipients on cyclosporine.
Thirty-two children who had undergone liver transplantation were paired according to their posttransplantation duration, renal function, and diagnoses when possible and randomized either to continue nifedipine (NIF group) or switch to diltiazem (DIL group), in addition to continuing their usual immunosuppressive medications. The cases were followed prospectively regarding diltiazem tolerance, cyclosporine dose requirements, effect on cyclosporine kinetics, diltiazem kinetics, as well as effect on renal function. Diltiazem was well tolerated at a dose of 3 mg to 6.4 mg/kg/day (max 180 mg/day) with infrequent self-limited mild side effects. Cyclosporine daily dose was reduced by a mean of 36.7% and 38.3% at 3 and 6 months, respectively, in the DIL group to achieve target trough cyclosporine levels without modifying liver function. No significant difference in renal function was observed after 3 to 6 months in either group based on blood urea nitrogen and creatinine levels and glomerular filtration rate by the DTPA method. Diltiazem appears to be well tolerated in children and allows for substantial dose reductions of CSA without apparent effects on liver graft function.
al Edreesi
M
M
Montreal Pediatric Liver Transplant Program, Hôpital Ste-Justine, Montreal, Quebec, Canada.
Caillé
G
G
Dupuis
C
C
Théoret
Y
Y
Paradis
K
K
D000293:Adolescent; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000378:metabolism; D016572:Cyclosporine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004110:Diltiazem / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008099:Liver / Q000378:metabolism*; D016031:Liver Transplantation; D008297:Male; D011446:Prospective Studies; D012449:Safety; D016896:Treatment Outcome
D002121:Calcium Channel Blockers; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D004110:Diltiazem