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New tablet formulation of tacrolimus with smaller interindividual variability may become a better treatment option than the conventional capsule formulation in organ transplant patients

Authors Kim YK, Kim A, Park SJ, Lee H

Received 19 May 2017

Accepted for publication 29 August 2017

Published 28 September 2017 Volume 2017:11 Pages 2861—2869

DOI https://doi.org/10.2147/DDDT.S142201

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lucy Goodman

Peer reviewer comments 2

Editor who approved publication: Dr Qiongyu Guo

Yu Kyong Kim,1 Anhye Kim,1,2 Shin Jung Park,3 Howard Lee1,4

1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Clinical Trial Center, Ajou University Medical Center, Suwon, 3Research Institute, Chong Kun Dang Pharmaceutical Corp, Yongin, 4Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Suwon, Republic of Korea

Abstract: To evaluate the pharmacokinetic (PK) and tolerability profiles of a new tablet formulation of tacrolimus and its interindividual variability (IIV) in the systemic exposure, and to compare them with those of the conventional capsule formulation, a randomized, open-label, two-treatment, two-period, two-sequence, crossover study was performed in 47 healthy males. The capsule or tablet formulation of tacrolimus was orally administered, and serial blood samples were collected up to 96 hours after dosing. Whole-blood tacrolimus concentration was determined using liquid chromatography–tandem mass spectrometry. The maximum whole-blood tacrolimus concentration (Cmax) and the area under the whole-blood tacrolimus concentration–time curve from 0 hour to the last quantifiable concentration (AUClast) were compared between the two formulations. The similarity factor (f2) of the in vitro dissolution profiles was calculated. The geometric mean ratio (90% confidence interval) of tablet to capsule was 0.9680 (0.8873–1.0560) and 1.0322 (0.9359–1.1385) for Cmax and AUClast, respectively. The IIV of Cmax and AUClast of the tablet was smaller than the capsule. The f2 values were >50 in all media. Both formulations were well tolerated. Thus, the tablet formulation of tacrolimus has smaller IIV in the systemic exposure than capsule, while having comparable PK and tolerability profiles, which may render it as a better treatment option for organ transplant patients.

Keywords: new formulation, incrementally modified drug, comparative pharmacokinetics, healthy volunteers, immunosuppressant

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