Mycophenolate pharmacokinetics in early period following lung or heart transplantation.
BACKGROUND
The available pharmacokinetic and pharmacodynamic data on mycophenolic acid (MPA), the pharmacologically active metabolite of mycophenolate mofetil (MMF), are derived largely from renal transplant patients, not thoracic transplant recipients.


OBJECTIVE
To evaluate, in a pilot study, the pharmacokinetics of MPA at 3 different times in the early period (up to the first 9 mo) following lung or heart transplantation.


METHODS
Nine patients were entered into this open-label study. Upon administration of a steady-state morning MMF dose, blood samples were collected at 0, 20, 40, 60, and 90 minutes and at 2, 4, 6, 8, 10, and 12 hours after the dose at 3 times (denoted as sampling periods 1, 2, and 3) in the early posttransplant period. Total MPA concentrations were measured by a validated HPLC method with ultraviolet detection and followed by ultrafiltration of pooled samples for unbound MPA concentrations. Pharmacokinetic parameters (maximal concentration [C(max)], dose-normalized C(max), time to C(max), minimum concentration, predose concentration, AUC, dose-normalized AUC, free fraction, free AUC) were calculated by traditional noncompartmental methods.


RESULTS
Patient characteristics included 7 men and 2 women, 5 lung and 4 heart transplant recipients, mean +/- SD age 53 +/- 11 years, and weight 77 +/- 14 kg. All patients were receiving prednisone and cyclosporine (with the exception of 2 pts. on tacrolimus during sampling periods 2 and 3). Sampling periods 1, 2, and 3 occurred on posttransplant days 15 +/- 13, 56 +/- 33, and 125 +/- 73, respectively. No significant differences were found between sampling periods in any pharmacokinetic parameter. Drug exposure as evaluated by AUC was 39.95 +/- 44.86, 25.24 +/- 25.68, and 43.96 +/- 38.67 micro g*h/mL during sampling periods 1, 2, and 3, respectively, (p > 0.05).


CONCLUSIONS
As of September 26, 2003, this is the first study to systematically evaluate MPA pharmacokinetics in thoracic transplant recipients at 3 different time points during the early posttransplant period. Wide interpatient variability in MPA pharmacokinetics was observed, thus emphasizing the need to individualize dosing of MMF and to further evaluate important pharmacokinetic/pharmacodynamic parameters and endpoints that impact on clinical outcomes. Further studies involving more patients and pharmacodynamic outcomes are underway to help identify optimal MMF strategies.
Ensom
Mary H H
MH
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada and Clinical Pharmacy Specialist, Pharmacy Department, Children's & Women's Health Centre of British Columbia. ensom@interchange.ubc.ca
Partovi
Nilufar
N
Decarie
Diane
D
Ignaszewski
Andrew P
AP
Fradet
Guy J
GJ
Levy
Robert D
RD
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D019540:Area Under Curve; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy; D016027:Heart Transplantation / Q000706:statistics & numerical data*; D006801:Humans; D016040:Lung Transplantation / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010865:Pilot Projects; D013997:Time Factors
D009173:Mycophenolic Acid