Tacrolimus induces remission in refractory and relapsing lupus nephritis by decreasing P-glycoprotein expression and function on peripheral blood lymphocytes

Edavalath, Sukesh; Kumar, Mandhir; Gupta, Vikas; Mishra, Ravi; Misra, Durga Prasanna; Gupta, Latika; Agarwal, Vikas

doi:10.1007/s00296-021-05057-1

Cited by 12 publications

(4 citation statements)

References 37 publications

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“…The mechanism of herb-drug interaction between deoxyschizandrin and Tac has not been conclusively determined, and current studies only generally indicate that Wuzhi capsule could inhibited P-gp-mediated efflux ( Qin et al, 2010a ; Qin et al, 2010b ) and CYP3A-mediated metabolism ( Chen et al, 2020 ; Kou et al, 2022 ) of Tac, which resulted in an increased systemic exposure of Tac. These studies consider that Tac is a substrate of P-gp, and is mainly metabolized by cytochrome CYP3A in the liver and the small intestine ( Picchianti-Diamanti et al, 2014 ; Krogstad et al, 2018 ; Prytuła et al, 2019 ; Edavalath et al, 2022 ); so, if drugs that affect the activity of P-gp or CYP3A may influence the pharmacokinetics of Tac ( Wen et al, 2023 ). Previously published paper has shown that several constituents from Wuzhi capsule could inhibited activity of P-gp and CYP3A ( Xue et al, 2013 ; Chen et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic assessment of tacrolimus in combination with deoxyschizandrin in rats

Sun,

Wang,

Liu

et al. 2024

Front. Pharmacol.

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BackgroundTacrolimus (Tac) is commonly used for postoperative immunosuppressive therapy in transplant patients. However, problems, for example, low bioavailability and unstable plasma concentration, persist for a long time, Studies have reported that the deoxyschizandrin could effectively improve these problems, but the pharmacokinetic parameters (PKs) of Tac combined with deoxyschizandrin are still unknown.MethodIn this study, an UHPLC-MS/MS method has been established for simultaneous quantitation of Tac and deoxyschizandrin. The PKs of Tac influenced by different doses of deoxyschizandrin after single and multiple administrations were analyzed, and the different impact of deoxyschizandrin and Wuzhi capsule on PKs of Tac were compared.ResultThe modified UHPLC-MS/MS method could rapid quantification of Tac and deoxyschizandrin within 2 min using bifendatatum as the internal standard (IS). All items were successfully validated. The Cmax of deoxyschizandrin increased from 148.27 ± 23.20 to 229.13 ± 54.77 ng/mL in rats after multiple administrations for 12 days. After co-administration of 150 mg/mL deoxyschizandrin, Tac had an earlier Tmax and greater Cmax and AUC0–t, and the Cmax and AUC0–t of Tac increased from 14.26 ± 4.73 to 54.48 ± 14.37 ng/mL and from 95.10 ± 32.61 to 315.23 ± 92.22 h/ng/mL, respectively; this relationship was positively proportional to the dosage of deoxyschizandrin. In addition, compared with Wuzhi capsule, the same dose of deoxyschizandrin has a better effective on Tac along with more stable overall PKs.ConclusionAn UHPLC-MS/MS method was established and validated for simultaneous detection of deoxyschizandrin and Tac. Deoxyschizandrin could improve the in vivo exposure level and stability of Tac, besides, this effect is better than Wuzhi capsule in same dose.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic assessment of tacrolimus in combination with deoxyschizandrin in rats

Sun,

Wang,

Liu

et al. 2024

Front. Pharmacol.

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“…The lack of accessibility of biologics in India (due to costs as well as heightened risk of opportunistic infections such as tuberculosis) might have resulted in the use of tacrolimus as a csDMARD in a considerable proportion of TAK patients from India. Such use has been extrapolated from the use of tacrolimus in treatment-refractory rheumatoid arthritis or systemic lupus erythematosus in studies from Asia [ 57 , 58 ]. Limited in-vitro evidence suggests the potential utility of tacrolimus as a DMARD in TAK [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of Geographic Location on Diagnosis and Initial Management of Takayasu Arteritis: A Tale of Two Cohorts from Italy and India

et al. 2022

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The present study compares disease characteristics, imaging modalities used, and patterns of treatment in two large cohorts of Takayasu arteritis (TAK) from Italy and India. Clinic files were retrospectively reviewed to retrieve information about initial choices of vascular imaging and immunosuppressive therapies. Unpaired t-tests compared means, and proportions were compared using Fisher’s exact test or Chi square test [Odds ratios (OR) with 95% confidence intervals (95%CI) calculated where appropriate]. The cohorts comprised 318 patients [Italy (n = 127), India (n = 191)] with similar delays to diagnosis. Ultrasound (OR Italy vs. India 9.25, 95%CI 5.02–17.07) was more frequently used in Italy and CT angiography in India (OR 0.32, 95%CI 0.20–0.51). Corticosteroid use was more prevalent and for longer duration in Italy. TAK from Italy had been more often treated with methotrexate, leflunomide or azathioprine, as opposed to tacrolimus in TAK from India (p < 0.05). Biologic or targeted synthetic disease-modifying agents were almost exclusively used in Italy. Survival on first immunosuppressive agent was longer from Italy than from India (log rank test p value 0.041). Considerable differences in the choice of initial vascular imaging modality and therapies for TAK from Italy and India could relate to prevalent socio-economic disparities. These should be considered while developing treatment recommendations for TAK.

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“…Recent research suggests that tacrolimus could offer a safer and superior therapeutic approach for managing patients with refractory and recurrent LN. A portion of this benefit is attributed to the alleviation of P-gp-mediated glucocorticoid resistance ( Edavalath et al, 2022 ). Tacrolimus acts as a P-gp inhibitor with a dual mode of action to reduce P-gp activity.…”

Section: Non-immune Mechanismmentioning

confidence: 99%

Mechanism of tacrolimus in the treatment of lupus nephritis

Wang,

Zhou,

Niu

et al. 2024

Front. Pharmacol.

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Systemic lupus erythematosus (SLE) is a complex autoimmune disorder, with more than half of the patients developing lupus nephritis (LN), which significantly contributes to chronic kidney disease (CKD) and end-stage renal disease (ESRD). The treatment of lupus nephritis has always been challenging. Tacrolimus (TAC), an effective immunosuppressant, has been increasingly used in the treatment of LN in recent years. This review aims to explore the mechanisms of action of tacrolimus in treating LN. Firstly, we briefly introduce the pharmacological properties of tacrolimus, including its role as a calcineurin (CaN) inhibitor, exerting immunosuppressive effects by inhibiting T cell activation and cytokine production. Subsequently, we focus on various other immunomodulatory mechanisms of tacrolimus in LN therapy, including its effects on T cells, B cells, and immune cells in kidney. Particularly, we emphasize tacrolimus’ regulatory effect on inflammatory mediators and its importance in modulating the Th1/Th2 and Th17/Treg balance. Additionally, we review its effects on actin cytoskeleton, angiotensin II (Ang II)-specific vascular contraction, and P-glycoprotein activity, summarizing its impacts on non-immune mechanisms. Finally, we summarize the efficacy and safety of tacrolimus in clinical studies and trials. Although some studies have shown significant efficacy of tacrolimus in treating LN, its safety remains a challenge. We outline the potential adverse reactions of long-term tacrolimus use and provide suggestions on effectively monitoring and managing these adverse reactions in clinical practice. In general, tacrolimus, as a novel immunosuppressant, holds promising prospects for treating LN. Of course, further research is needed to better understand its therapeutic mechanisms and ensure its safety and efficacy in clinical practice.

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Tacrolimus induces remission in refractory and relapsing lupus nephritis by decreasing P-glycoprotein expression and function on peripheral blood lymphocytes

Cited by 12 publications

References 37 publications

Pharmacokinetic assessment of tacrolimus in combination with deoxyschizandrin in rats

Pharmacokinetic assessment of tacrolimus in combination with deoxyschizandrin in rats

Impact of Geographic Location on Diagnosis and Initial Management of Takayasu Arteritis: A Tale of Two Cohorts from Italy and India

Mechanism of tacrolimus in the treatment of lupus nephritis

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