Mycophenolic acid levels in pediatric heart transplant recipients receiving mycophenolate mofetil.
BACKGROUND
Mycophenolate mofetil (MMF) is an immunosuppressive agent that has shown promise in adult patients who have undergone heart transplantation. There have been a number of studies of the pharmacokinetics of MMF in adult solid organ transplant recipients, but there is very little information in the pediatric population. The purpose of this study was to review our experience with MMF dosing and the role of mycophenolic acid (MPA) levels for therapeutic drug monitoring in a population of pediatric heart transplant recipients.


METHODS
Data were obtained by review of the pediatric heart transplant database between November 1, 1997 and October 15, 1998. The data included all serum trough MPA levels, patient age, weight, height, indication for and dose of MMF, other medications, and details of all episodes of graft rejection.


RESULTS
Forty-four patients (27 males) had a total of 128 serum trough MPA levels. Median age at transplant was 2.7 years (7 days to 18.4 years), and at time of review was 6.3 years (29 days to 23.5 years). MMF treatment was used for induction in 18 patients, induction and rejection in 23 patients and graft vasculopathy in 3 patients. Dosing by body surface area (mg/m(2)), age and interval from transplantation were all independently associated with MPA level. There was a trend toward requiring higher doses to achieve desired levels (>3 ng/ml) in younger patients. The average dose to achieve desired levels was higher in the immediate post-transplant period. There was a trend that MPA levels for a given dose were higher in patients on concurrent tacrolimus therapy.


CONCLUSIONS
(1) There is marked individual variation in pharmacokinetics of MMF in pediatric patients; (2) dosing by body surface area may be advantageous; (3) higher MMF doses may be required at younger ages and in the early period after transplantation; (4) lower MMF doses may be required with concurrent tacrolimus therapy; and (5) serum trough MPA levels may relate to efficacy. Therefore, therapeutic drug monitoring of serum trough MPA levels may be required for individualized MMF dosing in pediatric cases.
Dipchand
A I
AI
Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada. anne.dipchand@sickkids.on.ca
Pietra
B
B
McCrindle
B W
BW
Rosebrook-Bicknell
H L
HL
Boucek
M M
MM
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics; D016903:Drug Monitoring / Q000379:methods; D006084:Graft Rejection / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D007223:Infant; D007231:Infant, Newborn; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood* / Q000276:immunology / Q000493:pharmacokinetics*; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics; D014180:Transplantation
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus