Dataset Information

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

ABSTRACT: Sirolimus is an effective oral treatment for pediatric patients with lymphangioma. The present clinical study in 15 children (0.12-16.39 years of age) examines the effects of underlying factors on sirolimus concentrations through application of a population pharmacokinetic model. Using Monte Carlo simulation, an initial dose regimen for sirolimus in pediatric patients with lymphangioma is presented. It is found that the lower the body weight, the higher the clearance rate and sirolimus clearances are 0.31-0.17 L/h/kg in pediatric patients with lymphangioma whose weights are 5-60 kg, respectively. The doses of sirolimus, 0.07, 0.06, 0.05 mg/kg/day are recommended for weights of 5-10, 10-24.5 and 24.5-60 kg in children with lymphangioma. This study is the first to establish a population pharmacokinetic model for sirolimus and to recommend initial doses in pediatric patients with lymphangioma. Large scale, prospective studies are needed in the future.

SUBMITTER: Chen X

PROVIDER: S-EPMC8606893 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Chen Xiao X Wang Dongdong D Wang Guangfei G Huang Yidie Y Yu Xin X Lu Jinmiao J Zhai Xiaowen X Xu Hong H Li Zhiping Z

Frontiers in pharmacology 20211108

Sirolimus is an effective oral treatment for pediatric patients with lymphangioma. The present clinical study in 15 children (0.12-16.39 years of age) examines the effects of underlying factors on sirolimus concentrations through application of a population pharmacokinetic model. Using Monte Carlo simulation, an initial dose regimen for sirolimus in pediatric patients with lymphangioma is presented. It is found that the lower the body weight, the higher the clearance rate and sirolimus clearance ...[more]

PMID: 34819851

Similar Datasets

Project description:The narrow therapeutic index and large interpatient variability in sirolimus pharmacokinetics (PK) make therapeutic drug monitoring necessary. Factors responsible for PK variability are not well understood, and published PK studies do not include pediatric patients with neurofibromatosis type 1 (NF1). The objectives of this study were to estimate sirolimus clearance in a cohort of children with NF1 using data collected in a concentration-guided trial, to evaluate the effect of treatment duration on clearance and dose requirements, and to evaluate the association of sirolimus clearance with patient-specific factors, including age, weight, body surface area (BSA), race, and sex.Sirolimus concentration-time data were collected from an ongoing prospective trial in children with NF1. An iterative 2-stage Bayesian method was used for the PK parameter analyses.Data from 44 patients with NF1 were included in the analyses. Mean age was 8.4 years (SD 4.5, range 3-18), and mean weight was 29.8 kg (SD 16.7, range 12-85.8). Mean sirolimus clearance was 11.8 L/h (SD 4.6, range 2.2-24.1), and the mean dose to obtain a target trough concentration of 10-15 ng/mL was 2.0 mg/m administered twice daily (SD 0.72, range 0.77-3.85). A nonlinear relationship between age and clearance was observed. Total body weight and BSA were strong predictors of sirolimus clearance (r = 0.67 and 0.65, respectively).Sirolimus clearance in children with NF1 is comparable with that in pediatric transplant patients. Clearance was most associated with body size parameters (BSA and total body weight) in children with NF1. When normalized for size, an age effect on clearance was observed in the youngest patients, most likely because of the maturational changes in drug absorption and metabolism. A mean dose of 2.0 mg/m twice a day was required for attainment of target trough concentrations of 10-15 ng/mL in children greater than 3 years of age who have NF1. The updated model will allow PK-guided individualized dosing of sirolimus in patients with NF1.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets