Evaluation of limited sampling strategies for estimation of 12-hour mycophenolic acid area under the plasma concentration-time curve in adult renal transplant patients

Citation
C. Willis et al., Evaluation of limited sampling strategies for estimation of 12-hour mycophenolic acid area under the plasma concentration-time curve in adult renal transplant patients, THER DRUG M, 22(5), 2000, pp. 549-554
Citations number
28
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
THERAPEUTIC DRUG MONITORING
ISSN journal
01634356 → ACNP
Volume
22
Issue
5
Year of publication
2000
Pages
549 - 554
Database
ISI
SICI code
0163-4356(200010)22:5<549:EOLSSF>2.0.ZU;2-1
Abstract
Mycophenolate mofetil, the oral prodrug of mycophenolic acid, is indicated as immunosuppressive therapy after renal transplantation. To aid in the inv estigation 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 mycophenol ic acid area under the concentration-time curve (AUC). In the current study , the authors investigated the predictive performance of six published mode ls to estimate AUG. A total of 49 profiles from 25 renal transplant patient s were used to test each model's performance against a full 14 time-paint A UG. A wide range of agreement was found when predicted AUCs were compared w ith full AUCs using linear regression analysis (range: r(2) = 0.499 to 0.83 6). Model 1, which uses 4 time-points over 6 hours, was found to be superio r to all Ether models. The range of time-points used in this model takes in to 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 conc entration in these patients. Caution is warranted when using limited sampli ng strategies on patients whose absorption of mycophenolic acid is altered, compared with those of the pharmacokinetic profiles from which the model w as developed.