Evaluation of limited sampling strategies for estimation of 12-hour mycophenolic acid area under the plasma concentration-time curve in adult renal transplant patients.
Mycophenolate mofetil, the oral prodrug of mycophenolic acid, is indicated as immunosuppressive therapy after renal transplantation. To aid in the investigation of pharmacokinetic-pharmacodynamic relationships of mycophenolic acid in the clinical setting, limited blood sampling strategies have been proposed, and models from these developed, for the estimation of mycophenolic acid area under the concentration-time curve (AUC). In the current study, the authors investigated the predictive performance of six published models to estimate AUC. A total of 49 profiles from 25 renal transplant patients were used to test each model's performance against a full 14 time-point AUC. A wide range of agreement was found when predicted AUCs were compared with full AUCs using linear regression analysis (range: r2 = 0.499 to 0.836). Model 1, which uses 4 time-points over 6 hours, was found to be superior to all other models. The range of time-points used in this model takes into account patients with variable absorption. This model should be further tested on data sets from other centers. The relatively poor performance of the other models may be caused by their inability to describe the peak concentration in these patients. Caution is warranted when using limited sampling strategies on patients whose absorption of mycophenolic acid is altered, compared with those of the pharmacokinetic profiles from which the model was developed.
Willis
C
C
School of Pharmacy, University of Queensland, St. Lucia, Brisbane QLD, Australia.
Taylor
P J
PJ
Salm
P
P
Tett
S E
SE
Pillans
P I
PI
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D015331:Cohort Studies; D016903:Drug Monitoring / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D016030:Kidney Transplantation; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015233:Models, Statistical; D009173:Mycophenolic Acid / Q000097:blood / Q000493:pharmacokinetics*; D011237:Predictive Value of Tests; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D009173:Mycophenolic Acid