Science Links Japan | Limited Sampling Strategy for Estimating Area under the Concentration Curve for Mycophenolic Acid in Renal Transplant Recipients with Co-administration of Tacrolimus.

Limited Sampling Strategy for Estimating Area under the Concentration Curve for Mycophenolic Acid in Renal Transplant Recipients with Co-administration of Tacrolimus.

Accession number;04A0078422

Title;Limited Sampling Strategy for Estimating Area under the Concentration Curve for Mycophenolic Acid in Renal Transplant Recipients with Co-administration of Tacrolimus.

Author; TODA T (Hokkaido Coll. Pharmacy, Hokkaido, Jpn) WATANABE H (Hokkaido Coll. Pharmacy, Hokkaido, Jpn) KUROSAWA N (Hokkaido Coll. Pharmacy, Hokkaido, Jpn) OWADA E (Hokkaido Coll. Pharmacy, Hokkaido, Jpn) ACHIWA K (Sapporo City General Hospital, Hokkaido, Jpn) YUHKI Y (Sapporo City General Hospital, Hokkaido, Jpn) TADANO K (Sapporo City General Hospital, Hokkaido, Jpn) TAKAHASHI Y (Sapporo City General Hospital, Hokkaido, Jpn) HARADA H (Sapporo City General Hospital, Hokkaido, Jpn)

Journal Title;Japanese Journal of Pharmaceutical Health Care and Sciences

Journal Code:Y0888A

ISSN:1346-342X

VOL.30;NO.1;PAGE.1-7(2004)

Figure&Table&Reference;FIG.2, TBL.5, REF.28

Pub. Country;Japan

Language;English

Abstract;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: 1250-2000mg/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 (.TAU.)) between morning and evening dosing. Regarding a relationship between AUC (.TAU.) and the MPA concentrations for each sampling point, despite the substantial variation in MPA pharmacokinetics, a significant correlation was found between C0 and AUC (.TAU.) (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 (.TAU.). From the above findings, we recommend the use of the formula AUC (.TAU.) (.MU.g 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. (author abst.)

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