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Updated: May 18, 2026
08:38
Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
Tacrolimus strongly inhibits multiple human UDP-glucuronosyltransferase (UGT) isoforms
Xiao-You Liu1, Zhong-Ze Fang, Pei-Pei Dong
1Department of Organ Transplantation, Zhujiang Hospital, Nanfang Medical University, Dalian, China.
Die Pharmazie
|September 29, 2012
Summary
Tacrolimus (tacro) strongly inhibits key human liver UDP-glucuronosyltransferase (UGT) enzymes, including UGT1A1, UGT1A3, UGT2B7, and UGT2B15. This inhibition may explain frequent drug-drug interactions observed with tacrolimus.
Area of Science:
- Pharmacology
- Drug Metabolism
- Enzyme Kinetics
Background:
- Tacrolimus (tacro) is an immunosuppressant with a narrow therapeutic index.
- Drug-drug interactions (DDIs) involving tacrolimus are clinically significant.
- UDP-glucuronosyltransferases (UGTs) are crucial enzymes in drug metabolism.
Purpose of the Study:
- To evaluate the inhibitory effects of tacrolimus on major human liver UGT isoforms.
- To determine the inhibition kinetics and parameters for tacrolimus-induced UGT inhibition.
Main Methods:
- In vitro incubation system using recombinant UGT isoforms.
- 4-methylumbelliferone (4-MU) as a nonspecific substrate.
- Dixon and Lineweaver-Burk plots for kinetic analysis.
Main Results:
- Tacrolimus exhibited concentration-dependent inhibition of UGT1A1, UGT1A3, UGT2B7, and UGT2B15.
- Competitive inhibition was observed for UGT1A1, UGT1A3, and UGT2B7.
- Noncompetitive inhibition was observed for UGT2B15.
- Inhibition kinetic parameters (Ki) were determined for each UGT isoform.
Conclusions:
- Tacrolimus significantly inhibits critical human liver UGT isoforms.
- The observed inhibition patterns provide mechanistic insight into tacrolimus-related DDIs.
- Understanding these interactions is vital for optimizing tacrolimus therapy and patient safety.
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