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First Dose Tacrolimus Level Is Better Than CYP3A5 Genotyping in Prediction of Target Tacrolimus Dose

N. Townamchai,1 W. Chancharoenthana,1 S. Wattanatorn,1 S. Vadcharavivad,2 P. Chariyavilaskul,3 A. Leelahavanichkul,4 Y. Avihingsanon,1 K. Praditpornsilpa.1

1Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
2Department of Pharmacy Practice, Chulalongkorn University, Bangkok, Thailand
3Pharmacokinetic Research Unit, Chulalongkorn University, Bangkok, Thailand
4Department of Microbiology, Chulalongkorn University, Bangkok, Thailand.

Meeting: 2015 American Transplant Congress

Abstract number: B268

Keywords: Immunosuppression, Kidney transplantation, Polymorphism

Session Information

Date: Sunday, May 3, 2015

Session Name: Poster Session B: Translational Genetics and Proteomics in Transplantation

Session Time: 5:30pm-6:30pm

 Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

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Background: Tacrolimus dose highly varies among Asian kidney transplant recipients. This can be explained by variety of CYP3A5 expression. CYP3A5 genotyping is highly recommended for patients receiving tacrolimus. Here, we assessed the tacrolimus dose prediction by comparing CYP3A5 expression and tacrolimus dosage using tacrolimus concentration after single dose administration prior to kidney transplantation.

Method: Plasma tacrolimus trough level was measured at 12 hours after first dose of 0.1 mg/kg (TacC12), orally administered in 51 new kidney transplant recipients. Patients with CYP3A5 inhibitor/inducer co-medications were excluded. Genotyping for CYP3A5 expression were carried out by RT-PCR. The dosages of tacrolimus at post-operative day 7 and dosage which provided stable therapeutic levels in post-operative month 1 to 3 (C0 5-8 ng/mL) were recorded.

Results: There were 7, 25, and 19 patients with genotype of CYP3A5*1/*1, *1/*3, and *3/*3, respectively. The CYP3A5 genotypes significantly correlate with target tacrolimus dose at day 7 and the stable dose at 1- to 3- months (r = -0.52, p<0.05 and r = -0.59, p<0.05, respectively). The TacC12 better correlate with dosage of both tacrolimus dose at day 7 and stable dose at 1- to 3- months than CYP3A5 genotypes (r = -0.70, p < 0.05 and r = -0.65, p < 0.05, respectively).Conclusion: The CYP3A5 genotypes is a good predictor for target tacrolimus dose in perioperative period and post-transplant 1- to 3-months. However, TacC12 is better in tacrolimus dose prediction. This can be explained by the TacC12 is already compensated for many factors affecting tacrolimus dose and the CYP3A5 genotyping can categorize recipient in to only three groups. TacC12 is an alternative to CYP3A5 genotyping.

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To cite this abstract in AMA style:

Townamchai N, Chancharoenthana W, Wattanatorn S, Vadcharavivad S, Chariyavilaskul P, Leelahavanichkul A, Avihingsanon Y, Praditpornsilpa K. First Dose Tacrolimus Level Is Better Than CYP3A5 Genotyping in Prediction of Target Tacrolimus Dose [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/first-dose-tacrolimus-level-is-better-than-cyp3a5-genotyping-in-prediction-of-target-tacrolimus-dose/. Accessed April 17, 2021.

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