Optimization of Initial Dose Regimen for Sirolimus in Pediatric Patients With Lymphangioma

Chen, Xiao; Wang, Dongdong; Wang, Guangfei; Huang, Yidie; Yu, Xin; Lu, Jinmiao; Zhai, Xiaowen; Xu, Hong; Li, Zhiping

doi:10.3389/fphar.2021.668952

Cited by 6 publications

(4 citation statements)

References 30 publications

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“…Other co-medications, such as glucocorticoids, mycophenolic acid, and omeprazole, were not included in the final model as covariates. Many studies had demonstrated a nonlinear relationship between drug clearance and body weight in pediatric patients, and it may be well-represented by allometric scaling using a coefficient of 0.75 for clearance and a coefficient of 1 for volume ( Anderson and Holford, 2008 , 2011 ; Chen et al, 2021 ). In addition, a one-compartment model was used to describe tacrolimus in the present study as all the tacrolimus concentrations evaluated were trough concentrations.…”

Section: Discussionmentioning

confidence: 99%

Effects of Posaconazole on Tacrolimus Population Pharmacokinetics and Initial Dose in Children With Crohn’s Disease Undergoing Hematopoietic Stem Cell Transplantation

et al. 2022

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The present study explored the effects of posaconazole on tacrolimus population pharmacokinetics (PPK) in children with Crohn’s disease (CD) undergoing hematopoietic stem cell transplantation (HSCT). Tacrolimus concentrations, physiological and biochemical factors, and concomitant medications from 51 CD children undergoing HSCT were used to establish a PPK model based on a nonlinear mixed-effect model. Steady-state concentrations of tacrolimus for children weighing less than 20 kg treated with different dose regimens were simulated by the Monte Carlo method. Weight and concomitant medications were included as covariates. At the same weight, the relative tacrolimus clearance was 1:0.43 in children without or with posaconazole. Compared to children not receiving posaconazole, the simulated tacrolimus steady-state concentrations at different doses for different body weights were all higher in children receiving posaconazole (p < 0.01). Furthermore, in children not receiving posaconazole, the dosage regimen with the best probability of achieving the target concentration was 0.6 mg/kg/day for children weighing 5–8.2 kg and 0.5 mg/kg/day for children weighing 8.2–20 kg, while for children receiving posaconazole, the best probability of reaching the target concentration of tacrolimus was a dosage regimen of 0.5 mg/kg/day for children weighing 5–20 kg. In conclusion, the PPK for tacrolimus was determined in children with CD undergoing HSCT for the first time. Co-treatment with posaconazole significantly increased tacrolimus concentrations, and we recommend a specific initial dose regimen for tacrolimus.

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Section: Discussionmentioning

confidence: 99%

Effects of Posaconazole on Tacrolimus Population Pharmacokinetics and Initial Dose in Children With Crohn’s Disease Undergoing Hematopoietic Stem Cell Transplantation

et al. 2022

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“…Мы впервые в нашей стране в периоде новорождённости применили иммуносупрессивную терапию сиролимусом при врождённом пороке развития лимфатической системы согласно клиническим рекомендациям [12][13][14]. Результаты успешного лечения врождённого ХП и хилоторакса сиролимусом в литературе описаны достаточно широко [19][20][21][22].…”

Section: Discussionunclassified

“…Мама ребёнка была информирована и подписала добровольное письменное согласие на введение препарата. Назначение препарата сиролимус было принято согласно клиническим рекомендациям, а также рекомендациям Международного общества по изучению сосудистых мальформаций и данным современных публикаций [12][13][14].…”

Section: описание клинического случаяunclassified

Successful immunosuppressive treatment of chyloperitoneum in the newborn infant with multiple congenital anomalies

Gurskaya

Наковкин

Fisenko

et al. 2022

RPJ

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A unique clinical case of a combination of malformations of the anterior abdominal wall (omphalocele of large size) and malformation of the lymphatic system (congenital chyloperitoneum) is presented. Each of these defects can lead to a fatal outcome, and the combination of them has greatly increased the risk of developing an unfavourable outcome. The use of immunosuppressive therapy with Sirolimus used for the first time during the newborn period made it possible to completely stop the chyloperitoneum. This clinical example shows that in the treatment of surgical patients with multiple congenital malformations, a multidisciplinary approach and observation is necessary for timely response to the patient’s condition.

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“…In tuberous sclerosis complex patients, the sirolimus range was 5–15 ng/ml ( Wang et al, 2020 ). In pediatric patients with lymphangioma, the sirolimus range was also 5–15 ng/ml ( Chen et al, 2021a ). We simulated two different situations based on whether the children were co-administered posaconazole or not.…”

Section: Discussionmentioning

confidence: 99%

Initial sirolimus dosage recommendations for pediatric patients with PIK3CD mutation-related immunodeficiency disease

Chen

Wang²,

Lan³

et al. 2022

Front. Pharmacol.

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Sirolimus is used to treat pediatric patients with PIK3CD mutation-related immunodeficiency disease. However, the initial dosages of sirolimus remain undecided. The present study aims to explore initial dosages in pediatric patients with PIK3CD mutation-related immunodeficiency disease. Pediatric patients with this disease were analyzed using the population pharmacokinetic (PPK) model and the Monte Carlo simulation. Body weight and concomitant use of posaconazole were included in the final PPK model, where, under the same weight, clearances of sirolimus were 1 : 0.238 between children without and children with posaconazole. Without posaconazole, the initial dosages of sirolimus were 0.07, 0.06, 0.05, and 0.04 mg/kg/day for body weights of 10–14, 14–25, 25–50, and 50–60 kg, respectively. With posaconazole, the initial dosages of sirolimus were 0.02 mg/kg/day for body weights of 10–60 kg. This is the first attempt to build a sirolimus PPK model for recommending initial dosages in children with PIK3CD mutation-related immunodeficiency disease, thereby providing a reference for individualized clinical drug administration.

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Optimization of Initial Dose Regimen for Sirolimus in Pediatric Patients With Lymphangioma

Cited by 6 publications

References 30 publications

Effects of Posaconazole on Tacrolimus Population Pharmacokinetics and Initial Dose in Children With Crohn’s Disease Undergoing Hematopoietic Stem Cell Transplantation

Effects of Posaconazole on Tacrolimus Population Pharmacokinetics and Initial Dose in Children With Crohn’s Disease Undergoing Hematopoietic Stem Cell Transplantation

Successful immunosuppressive treatment of chyloperitoneum in the newborn infant with multiple congenital anomalies

Initial sirolimus dosage recommendations for pediatric patients with PIK3CD mutation-related immunodeficiency disease

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