Optimizing the therapeutic window of sirolimus by monitoring blood concentration for the treatment of immune thrombocytopenia

Zhang, Yun; Quan, Yao; Wang, Dan; Cassady, Kaniel; Zou, Wenhang; Xiong, Jingkang; Yao, Han; Deng, Xiaojuan; Wang, Ping; Yang, Shijie; Zhang, Xi; Feng, Yimei

doi:10.1080/09537104.2023.2277831

Cited by 2 publications

(1 citation statement)

References 29 publications

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“…3 Sirolimus side effects include stomatitis, dyslipidemia, edema, respiratory infections, and cytopenias. [13][14][15] The current case reports a patient with significant improvement in the liver biochemistry after sirolimus and rituximab therapy. It is challenging to attribute the clinical improvement on sirolimus alone, but an 18-month remission free period after the last rituximab infusion makes a case for sirolimus significant role in controlling AIH.…”

Section: Discussionmentioning

confidence: 99%

Role of Sirolimus and Rituximab in the Treatment of Autoimmune Hepatitis

Zouridis,

Oo,

Syn

2024

ACG Case Rep J

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Autoimmune hepatitis (AIH) is a rare chronic liver disease affecting annually 100,000-200,000 individuals in the United States. The first-line therapy in AIH is azathioprine and corticosteroids. However, adverse events may occur, which can preclude disease remission. In these cases, mycophenolate, mercaptopurine, and tacrolimus can be used. Rituximab is offered in difficult to treat cases. Sirolimus is an alternative regimen. However, little is known about its use in AIH. This is a challenging case of “difficult to treat” AIH managed with sirolimus and rituximab, after multiple unsuccessful trials with other medications.

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Section: Discussionmentioning

confidence: 99%

Role of Sirolimus and Rituximab in the Treatment of Autoimmune Hepatitis

Zouridis,

Oo,

Syn

2024

ACG Case Rep J

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Population pharmacokinetic study in children with vascular anomalies: body weight as a key variable in predicting the initial dose and dosing frequency of sirolimus

Fan,

Guo,

Zhao

et al. 2024

Front. Pharmacol.

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BackgroundThe main challenges faced when using sirolimus in children with vascular anomalies (VAs) still include significant pharmacokinetic (PK) variability, uncertainty in the target concentration range, as well as inconsistencies in initial dosing and dosing frequency. The aim of this study is to establish a new population pharmacokinetic (PPK) model for children with VAs to guide the individualized use of sirolimus.MethodsA PPK study was performed using data from children with VAs who received sirolimus between July 2017 and April 2022. A nonlinear mixed-effect modeling with a one-compartment model structure was applied. Monte Carlo simulation was employed to propose specific dosing recommendations to achieve the target trough concentrations (Ctrough) of 5–15 ng/mL.ResultsIn total, 134 blood concentrations from 49 pediatric patients were used to characterize the sirolimus pharmacokinetics. Covariate analysis identified body weight (BW) as a significant factor affecting clearance (CL) in the final PPK model. The typical clearance rate and distribution volume, standardized to a BW of 16 kg, were 4.06 L/h (4% relative standard error, RSE) and 155 L (26% RSE), respectively. Optimal dosing regimens were simulated for different BWs. For a twice-daily regimen, the recommended doses were 0.05, 0.06, 0.07, and 0.08 mg/kg/day for BW of <10, 10–20, 20–40, and ≥40 kg, respectively; for a once-daily regimen, the recommended doses were 0.06, 0.07, 0.08, and 0.09 mg/kg/day for BW of <10, 10–30, 30–50, and ≥50 kg, respectively. Notably, sirolimus Ctrough could be maintained between 5–15 ng/mL across various dosing frequencies based on the recommended dosing regimen.ConclusionWe established a PPK model of sirolimus for children with VAs and proposed an initial dosing strategy. Integrating initial dose and medication frequency recommendations into sirolimus’ guidelines will broaden its clinical options and simplify the clinical management for childhood VAs.

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Optimizing the therapeutic window of sirolimus by monitoring blood concentration for the treatment of immune thrombocytopenia

Cited by 2 publications

References 29 publications

Role of Sirolimus and Rituximab in the Treatment of Autoimmune Hepatitis

Role of Sirolimus and Rituximab in the Treatment of Autoimmune Hepatitis

Population pharmacokinetic study in children with vascular anomalies: body weight as a key variable in predicting the initial dose and dosing frequency of sirolimus

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