Limited Sampling Strategy for Estimating Area under the Concentration Curve for Mycophenolic Acid in Renal Transplant Recipients with Co-administration of Tacrolimus
| Autor: | Kohji Tadano, Nahoko Kurosawa, Takaki Toda, Kazuhito Achiwa, Tetsuo Hirano, Yasushi Takahashi, Yoshimitsu Yuhki, Hiroshi Harada, Toshimori Seki, Hiroyuki Watanabe, Eiji Owada |
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| Rok vydání: | 2004 |
| Předmět: | |
| Zdroj: | Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences). 30:1-7 |
| ISSN: | 1882-1499 1346-342X |
| DOI: | 10.5649/jjphcs.30.1 |
| Popis: | To obtain an adequate immunosuppressive effect of mycophenolate mofetil (MMF), various equations have been used for estimating the area under the concentration curve (AUC) for mycophenolic acid (MPA) under a limited sampling strategy. Most of them, however, involved cyclosporine (CYA) -based immunosuppression. In this study, we measured chronological blood concentrations of MPA when included in tacrolimus (TAC, alternative calcineurin inhibitor) -based triple-drug immunosuppression in renal transplant recipients and investigated the effectiveness of a limited sampling strategy which minimized patients' inconvenience.Measurement of MPA concentrations in consecutive samplings over a 24-hour period in 6 renal transplant recipients receiving TAC-based triple-drug immunosuppression therapy (MMF dose : 1250-2000 mg/day, twice a day), showed substantial inter-patient and intra-patient variability in MPA pharmacokinetics. The second MPA peak was observed in 8 concentration profiles. There were no significant differences in Tmax, Tlag, dose-normalized Cmax, pre-dose concentration (C0), and AUC (0-12) (AUC (τ)) between morning and evening dosing.Regarding a relationship between AUC (τ) and the MPA concentrations for each sampling point, despite the substantial variation in MPA pharmacokinetics, a significant correlation was found between C0 and AUC (τ) (r2= 0.734). The highest r2 value was obtained at C8 (r2=0.852). The optimum combination of sampling time points for estimating AUC for MPA using stepwise linear regression was C0, C3, C8 (r2= 0.964) and this combination had the lowest maximum prediction error (22.6%) in the estimation of AUC (τ). From the above findings, we recommend the use of the formula AUC (τ) (μg·h/ mL) = 7.82 +3.58· C0 + 1.87· C3 + 7.15 ·C8 for estimating the AUC for MPA in renal transplant recipients also receiving TAC. |
| Databáze: | OpenAIRE |
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