Tacrolimus therapy causes hepatotoxicity in patients with a history of liver disease

Ko, Myong Suk; Choi, Young Hee; Lee, Jenny Sue; Kim, Hyang Sook; Lee, Chang Ho; Kim, Sang Geon

doi:10.5414/cp202226

Cited by 15 publications

(3 citation statements)

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“…[16][17][18] Wuzhi capsule, a traditional Chinese medicine (registration number in China: Z10983013), is often prescribed to alleviate the hepatotoxicity of tacrolimus in China. [19][20][21] Wuzhi capsule has been reported to increase tacrolimus exposure, leading to further dose reduction of approximately 50% or more. 22,23 Pharmacokinetic studies 24,25 have showed that co-treatment with Wuzhi capsule can reduce the clearance rate, peak concentration, and peak time delay of tacrolimus.…”

Section: Introductionmentioning

confidence: 99%

Wuzhi Capsule Dosage Affects Tacrolimus Elimination in Adult Kidney Transplant Recipients, as Determined by a Population Pharmacokinetics Analysis

Chen¹,

Yang²,

Wang³

et al. 2021

PGPM

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Purpose In this study, we aimed to establish a tacrolimus population pharmacokinetic model and better understand the drug-drug interaction between Wuzhi capsule and tacrolimus in Chinese renal transplant recipients. Patients and Methods We performed a population pharmacokinetic analysis using a non-linear mixed-effects model to determine the suitable Wuzhi capsule dose in combination with tacrolimus. Data on 1378 tacrolimus steady-state concentrations were obtained from 142 patients who received kidney transplant in Changhai Hospital and Huashan Hospital. Demographic characteristics, laboratory tests, genetic polymorphisms, and co-medications were evaluated. Results The one-compartment model best described data. Our final model identified creatinine clearance rate, hematocrit, Wuzhi capsule dose, CYP3A5*3 genetic polymorphisms, and tacrolimus daily dose as significant covariates for tacrolimus clearance, with the value of 14.4 L h −1 , and the between-subject variability (BSV) was 25.4%. The Wuzhi capsule showed a dose-dependent effect on tacrolimus pharmacokinetics, demonstrating a stronger inhibitory effect than inductive effect. Conclusion Our model can accurately describe population pharmacokinetics of tacrolimus when combined with different doses of Wuzhi capsule. Additionally, this model can be used for individualizing tacrolimus dose following kidney transplantation.

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Section: Introductionmentioning

confidence: 99%

Wuzhi Capsule Dosage Affects Tacrolimus Elimination in Adult Kidney Transplant Recipients, as Determined by a Population Pharmacokinetics Analysis

Chen¹,

Yang²,

Wang³

et al. 2021

PGPM

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“…It has a narrow therapeutic window so that therapeutic drug monitoring is recommended for the patients receiving tacrolimus. Furthermore, long‐term use of tacrolimus can cause liver damage such as elevation of alanine aminotransferase (ALT) and total bilirubin level . In China, a traditional Chinese medicine named Wuzhi is often prescribed to patients to alleviate the hepatotoxicity of tacrolimus .…”

mentioning

confidence: 99%

Prediction of Drug–Drug Interaction between Tacrolimus and Principal Ingredients of Wuzhi Capsule in Chinese Healthy Volunteers Using Physiologically‐Based Pharmacokinetic Modelling

Zhang

et al. 2017

Basic Clin Pharma Tox

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Schisantherin A and schisandrin A, the most abundant active ingredients of Wuzhi capsule, are known to inhibit tacrolimus metabolism by inhibiting CYP3A4/5. We aimed to predict the contribution of schisantherin A and schisandrin A to drug-drug interaction (DDI) between Wuzhi capsule and tacrolimus using physiologically-based pharmacokinetic (PBPK) modelling. Firstly, the inhibition mechanism of schisantherin A and schisandrin A on CYP3A4/5 was investigated. Thereafter, PBPK models of schisantherin A, schisandrin A and tacrolimus were established. Finally, tacrolimus pharmacokinetics were evaluated after the combined use with schisantherin A or schisandrin A. The blood area under the curve (AUC) of tacrolimus increased 1.77- and 2.61-fold after a single dose and multiple doses of schisantherin A, respectively. Meanwhile, schisandrin A inhibited tacrolimus metabolism to a smaller extent. Also, it showed that mechanism-based inhibition (MBI) played a more important role in DDI than reversible inhibition after long-term administration, while reversible inhibition was comparable to MBI after single-dose administration. In conclusion, we utilized PBPK modelling to quantify the contribution of schisantherin A and schisandrin A to DDI between tacrolimus and Wuzhi capsule. This may provide more insights for the rational use of this drug combination.

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“…It indicates that Fk506 is most likely to cause impaired liver function in this event. And according to Ko reports [12], patients who had underlying liver disease should closely monitor the changes in liver function when treated with FK506.…”

Section: Hepatotoxicitymentioning

confidence: 99%

Adverse reactions and toxic side effects of Tacrolimus

Zhu

2022

International Conference on Biomedical and Intelligent Systems (IC-BIS 2022)

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Tacrolimus (FK506) is a novel macrolide antibiotic derived from the broth medium of soil fungi, which has a strong immune inhibitory effect, but its adverse reactions toxic side effects cannot be ignored. The side effects of tacrolimus may cause other clinical symptoms that directly or indirectly harm the patient. Under- standing the toxic side effects and adverse effects can provide valuable reference for clinical applications. The purpose of this article is to outline and summarize the potential side effects of tacrolimus toxicity, and briefly analyses the factors that lead to their creation. This work can provide a basis for clinical and follow-up studies.

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Tacrolimus therapy causes hepatotoxicity in patients with a history of liver disease

Abstract: Results indicate that tacrolimus may have a higher risk of inducing liver injury in Korean patients with a history of liver disease and may require close monitoring.

Cited by 15 publications

References 0 publications

Wuzhi Capsule Dosage Affects Tacrolimus Elimination in Adult Kidney Transplant Recipients, as Determined by a Population Pharmacokinetics Analysis

Wuzhi Capsule Dosage Affects Tacrolimus Elimination in Adult Kidney Transplant Recipients, as Determined by a Population Pharmacokinetics Analysis

Prediction of Drug–Drug Interaction between Tacrolimus and Principal Ingredients of Wuzhi Capsule in Chinese Healthy Volunteers Using Physiologically‐Based Pharmacokinetic Modelling

Adverse reactions and toxic side effects of Tacrolimus

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