Population Pharmacokinetic Analysis and Dosing Optimization of Sirolimus in Children With Tuberous Sclerosis Complex

Li, Sichan; Zhan, Min; Wu, Sanlan; Liao, Jianxiang; Xu, Huibi; Sun, Dan; Zhao, Xia; Wang, Yang

doi:10.1002/jcph.2033

Cited by 4 publications

(1 citation statement)

References 35 publications

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“…Ni et al reported population pharmacokinetics of ciclosporin in Chinese children with aplastic anemia: effects of weight, renal function, and stanozolol administration, the Ka of ciclosporin was fixed at 0.68/h ( Ni et al, 2013 ). Li et al reported population pharmacokinetic analysis and dosing optimization of sirolimus in children with tuberous sclerosis complex; the Ka of sirolimus was fixed at 0.7521/h ( Li et al, 2022 ).…”

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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Population pharmacokinetic analysis of sirolimus in Japanese pediatric and adult subjects receiving tablet or granule formulations

Miyazaki,

Hayashi,

Nozawa

et al. 2024

Drug Metabolism and Pharmacokinetics

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Remedial Dosing Recommendations for Sirolimus Delayed or Missed Dosages Caused by Poor Medication Compliance in Pediatric Tuberous Sclerosis Complex Patients

Yang,

Jiang,

Zhu

et al. 2024

CPD

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Background:: Delayed or missed dosages caused by poor medication compliance significantly affected the treatment of diseases in children. Aims:: The present study aimed to investigate the influence of delayed or missed dosages on sirolimus pharmacokinetics (PK) in pediatric tuberous sclerosis complex (TSC) patients and to recommend remedial dosages for nonadherent patients. Methods:: A published sirolimus population PK model in pediatric TSC patients was used to assess the influence of different nonadherence scenarios and recommend optimally remedial dosages based on Monte Carlo simulation. Thirteen nonadherent scenarios were simulated in this study, including delayed 2h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, 22 h, 23.5 h, and missed one dosage. Remedial dosing strategies contained 10-200% of scheduled dosages. The optimal remedial dosage was that with the maximum probability of returning the individual therapeutic range. Results:: For delayed or missed sirolimus dosages in pediatric TSC patients, when the delayed time was 0-8 h, 8-10 h, 10-18 h, 18-22.7 h, 22.7-24 h, 70%, 60%, 40%, 30%, 20% scheduled dosages were recommended to take immediately. When one dosage was missed, 120% of scheduled dosages were recommended at the next dose. Conclusion:: It was the first time to recommend remedial dosages for delayed or missed sirolimus therapy caused by poor medication compliance in pediatric TSC patients based on Monte Carlo simulation. Meanwhile, the present study provided a potential solution for delayed or missed dosages in clinical practice.

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Population Pharmacokinetic Analysis and Dosing Optimization of Sirolimus in Children With Tuberous Sclerosis Complex

Cited by 4 publications

References 35 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

Population pharmacokinetic analysis of sirolimus in Japanese pediatric and adult subjects receiving tablet or granule formulations

Remedial Dosing Recommendations for Sirolimus Delayed or Missed Dosages Caused by Poor Medication Compliance in Pediatric Tuberous Sclerosis Complex Patients

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