Mycophenolic acid pharmacokinetics in pediatric liver transplant recipients.
The aim of this study is to study mycophenolic acid (MPA) pharmacokinetics in stable pediatric liver transplant recipients and determine which times best represent the area under the concentration versus time curve (AUC) of MPA plasma concentrations. MPA pharmacokinetic profiles were determined in 21 liver transplant recipients (age, 2 to 15 years; 12 boys) administered mycophenolate mofetil (MMF) for at least 6 months. Ten patients were coadministered cyclosporine A (CsA), and 11 patients were coadministered tacrolimus (Tac). Plasma MPA levels were analyzed by enzyme-multiplied immunoassay technique in blood samples at 0, 0.33, 0.67, 1.25, 2, 3.5, 5, and 7 hours after MMF administration. The AUC of plasma concentrations to 7 hours (AUC(0-7)) was calculated using the linear trapezoidal rule. MPA plasma trough concentration (C(0)), maximal concentration, and AUC(0-7) values ranged 9- to 14-fold at a median of 1.81 mg/L (range, 0.4 to 3.7 mg/L), 10.5 mg/L (range, 2.8 to 40.0 mg/L), and 30.2 mg/L.hr (range, 9.3 to 80.3 mg/L.hr), respectively. AUC(0-7) correlated significantly with MMF dose (r = 0.552; P =.010) and C(0) (r = 0.844; P <.001). Median AUC(0-7) (29.6 v 31.4 mg/L.hr; P =.918) was similar in children comedicated with CsA or Tac. Median MMF dose was greater in the CsA group (500 v 250 mg; P =.006). Consequently, median AUC(0-7) was significantly lower in the CsA group when equalized for dose and body weight (2.02 v 3.85 microg/L.hr per mg of MMF dose per kg of weight; P =.002). Variations of MPA pharmacokinetics in pediatric liver transplant recipients suggest that monitoring MPA plasma levels is required. C(0) correlates closely with AUC. Comedication with CsA increased MMF dosage requirements compared with children on Tac therapy.
Aw
Marion M
MM
Institute of Liver Studies, King's College Hospital, London, UK.
Brown
Nigel W
NW
Itsuka
Toshi
T
Gonde
Christopher E
CE
Adams
Jemimah E
JE
Heaton
Nigel D
ND
Tredger
J Michael
JM
Mieli-Vergani
Giorgina
G
Dhawan
Anil
A
D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007223:Infant; D016031:Liver Transplantation; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009994:Osmolar Concentration; D011184:Postoperative Period; D011355:Prodrugs / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D011355:Prodrugs; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus