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A Limited Sampling Strategy to Estimate the Area Under the Concentration-Time Curve of Tacrolimus Modified-release Once-daily Preparation in Renal Transplant Recipients

Niioka, Takenori PhD*; Miura, Masatomo PhD*; Kagaya, Hideaki PhD*; Saito, Mitsuru MD, PhD; Numakura, Kazuyuki MD, PhD; Habuchi, Tomonori MD, PhD; Satoh, Shigeru MD, PhD†,‡

doi: 10.1097/FTD.0b013e31827efe37
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Objectives: The aim of this study was to develop a limited sampling strategy to estimate the area under the concentration-time curve (AUC) of a modified-release, once-daily formulation of tacrolimus (Advagraf, Japanese trade name Graceptor) with Japanese renal transplant patients.

Methods: Among the 43 enrolled patients, 23 patients continued to take Graceptor for 1 year. A total of 66 profiles on day 28 and day 365 from the 43 patients were randomly divided into a training group (N = 33) and a validation group (N = 33) without any overlap.

Results: The prediction formula for the AUC0–24 using the single C12h time point gave the highest correlation with the observed AUC0–24 (r2 = 0.9057). When 2 sampling times were used, C0hC12h were the best time points for the estimation of the AUC0–24 (AUC0–24 = 26.8 + 8.0C0h + 17.8C12h, r2 = 0.9221, P < 0.0001). There was no significant difference in the prediction error for the prediction formulas with the C0hC12h combination between CYP3A5 genotypes. The % mean prediction error, % mean absolute error, and % root mean squared prediction error of the prediction formula using C0hC12h were 0.1%, 7.6%, and 8.8%, respectively.

Conclusions: In a hospital setting, a limited sampling strategy using C0hC12h would be applicable to estimating the AUC0–24 of tacrolimus once daily.

Supplemental Digital Content is Available in the Text.

*Department of Pharmacy, Akita University Hospital

Department of Urology, Akita University School of Medicine

Division of Renal Replacement Therapeutic Science, Akita University School of Medicine, Akita, Japan.

Correspondence: Masatomo Miura, PhD, Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan (e-mail: m-miura@hos.akita-u.ac.jp).

The authors declare no conflict of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.drug-monitoring.com).

Received July 17, 2012

Accepted November 16, 2012

© 2013 by Lippincott Williams & Wilkins