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

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao Chen ◽  
Dongdong Wang ◽  
Guangfei Wang ◽  
Yidie Huang ◽  
Xin Yu ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Initial Dose ◽  
Dose Regimen ◽  
Population Pharmacokinetic Model ◽  
Large Scale ◽  
Pharmacokinetic Model ◽  
Pediatric Patients ◽  
Oral Treatment ◽  
The Body ◽  
Population Pharmacokinetic

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.

scholarly journals Population Pharmacokinetics and Dosing Optimization of Linezolid in Pediatric Patients

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Si-Chan Li ◽  
Qi Ye ◽  
Hua Xu ◽  
Long Zhang ◽  
Yang Wang
Keyword(s):  
Body Weight ◽  
Population Pharmacokinetics ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Pediatric Patients ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data ◽  
Nonparametric Bootstrap ◽  
Bootstrap Analysis ◽  
Final Model

ABSTRACT Linezolid is a synthetic antibiotic very effective in the treatment of infections caused by Gram-positive pathogens. Although the clinical application of linezolid in children has increased progressively, data on linezolid pharmacokinetics in pediatric patients are very limited. The aim of this study was to develop a population pharmacokinetic model for linezolid in children and optimize the dosing strategy in order to improve therapeutic efficacy. We performed a prospective pharmacokinetic study of pediatric patients aged 0 to 12 years. The population pharmacokinetic model was developed using the NONMEM program. Goodness-of-fit plots, nonparametric bootstrap analysis, normalized prediction distribution errors, and a visual predictive check were employed to evaluate the final model. The dosing regimen was optimized based on the final model. The pharmacokinetic data from 112 pediatric patients ages 0.03 to 11.9 years were analyzed. The pharmacokinetics could best be described by a one-compartment model with first-order elimination along with body weight and the estimated glomerular filtration rate as significant covariates. Simulations demonstrated that the currently approved dosage of 10 mg/kg of body weight every 8 h (q8h) would lead to a high risk of underdosing for children in the presence of bacteria with MICs of ≥2 mg/liter. To reach the pharmacokinetic target, an elevated dosage of 15 or 20 mg/kg q8h may be required for them. The population pharmacokinetics of linezolid were characterized in pediatric patients, and simulations provide an evidence-based approach for linezolid dosage individualization.

scholarly journals Pharmacokinetic Profile of a 2-Month Dose Regimen of Aripiprazole Lauroxil: A Phase I Study and a Population Pharmacokinetic Model

CNS Drugs ◽  
2017 ◽  
Vol 31 (7) ◽  
pp. 617-624 ◽  
Author(s):  
Marjie L. Hard ◽  
Richard J. Mills ◽  
Brian M. Sadler ◽  
Angela Y. Wehr ◽  
Peter J. Weiden ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Regimen ◽  
Phase I Study ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Pharmacokinetic Profile ◽  
Population Pharmacokinetic

scholarly journals Population Pharmacokinetics of Liposomal Amphotericin B in Pediatric Patients with Malignant Diseases

2006 ◽  
Vol 50 (3) ◽  
pp. 935-942 ◽  
Author(s):  
Ying Hong ◽  
Peter J. Shaw ◽  
Christa E. Nath ◽  
Satya P. Yadav ◽  
Katherine R. Stephen ◽  
...  
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Pediatric Oncology ◽  
Liposomal Amphotericin ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Pediatric Patients ◽  
Liposomal Amphotericin B ◽  
Population Pharmacokinetic ◽  
Malignant Diseases

ABSTRACT A population pharmacokinetic model of liposomal amphotericin B (L-AmB) in pediatric patients with malignant diseases was developed and evaluated. Blood samples were collected from 39 pediatric oncology patients who received multiple doses of L-AmB with a dose range from 0.8 to 5.9 mg/kg of body weight/day. The patient cohort had an average age of 7 years (range, 0.2 to 17 years) and weighed an average of 28.8 ± 19.8 kg. Population pharmacokinetic analyses were performed with NONMEM software. Pharmacokinetic parameters, interindividual variability (IIV), between-occasion variability (BOV), and intraindividual variability were estimated. The influence of patient characteristics on the pharmacokinetics of L-AmB was explored. The final population pharmacokinetic model was evaluated by using a bootstrap sampling technique. The L-AmB plasma concentration-time data was described by a two-compartment pharmacokinetic model with zero-order input and first-order elimination. The population mean estimates of clearance (CL) and volume of distribution in the central compartment (V 1) were 0.44 liters/h and 3.12 liters, respectively, and exhibited IIV (CL, 10%) and significant BOV (CL, 46% and V 1, 56%). The covariate models were CL (liters/h) = 0.44 · e 0.0152 · (WT − 21 ) and V 1 (liters) = 3.12 · e 0.0241  ·  (WT  −  21), where WT is the patient's body weight (kg) centered on the study population cohort median of 21 kg. Model evaluation by the bootstrap procedure indicated that the full pharmacokinetic model was robust and parameter estimates were accurate. In conclusion, the pharmacokinetics of L-AmB in pediatric oncology patients were adequately described by the developed population model. The model has been evaluated and can be used in the design of rational dosing strategies for L-AmB antifungal therapy in this special population.

Population pharmacokinetics of diethylcarbamazine in patients with lymphatic filariasis and healthy individuals

2021 ◽  
Author(s):  
Veenu Bala ◽  
Yashpal S Chhonker ◽  
Abdullah Alshehri ◽  
Constant Edi ◽  
Catherine M Bjerum ◽  
...  
Keyword(s):  
Body Weight ◽  
Lymphatic Filariasis ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Model Building ◽  
The Body ◽  
Population Pharmacokinetic ◽  
Healthy Individuals ◽  
Female Population ◽  
Final Population

Diethylcarbamazine (DEC) is a drug of choice to treat lymphatic filariasis (LF) either used alone or in combination as mass drug administration (MDA) preventive strategies. The objective of this study was to develop a population pharmacokinetic model for DEC in subjects infected with lymphatic filariasis (LF) compared to healthy individuals, and to evaluate the effect of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of DEC. This was an open-label cohort study of treatment naïve Wuchereria bancrofti -infected (n=32) and uninfected (n=24) adults residing in the Agboville district of Côte d’Ivoire. The population pharmacokinetic model for DEC was built using Phoenix NLME 8.0 software. The covariates included in the model building process were age, gender, bodyweight, infection status, creatinine clearance (CrCl), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. A total of 56 adults were enrolled in the study and a total of 728 samples were obtained over 168 hours. A one-compartment linear pharmacokinetic model with first-order absorption with an absorption lag-time (Tlag) best described the data. After determining the pharmacokinetics (PK) parameters of DEC, body weight and gender were found to be the significant covariates for DEC V/F. The final population pharmacokinetic model adequately described the pharmacokinetics of DEC in the studied population. Model-based simulation indicated that the body weight significantly impacted the exposure in both the male and female population. This analysis may further support the drug-drug interaction model development of DEC with different co-administered drugs/agents in disease control programs.

scholarly journals Population Pharmacokinetic Analysis of Amikacin for Optimal Pharmacotherapy in Korean Patients with Nontuberculous Mycobacterial Pulmonary Disease

Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 784
Author(s):  
Xuanyou Jin ◽  
Jaeseong Oh ◽  
Joo-Youn Cho ◽  
SeungHwan Lee ◽  
Su-jin Rhee
Keyword(s):  
Renal Function ◽  
Body Weight ◽  
Pulmonary Disease ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Compartment Model ◽  
The Body ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Properties

Amikacin is used as a therapy for patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) who are resistant to macrolide antibiotics or have severe symptoms. This study aimed to characterize the pharmacokinetic properties of amikacin in patients with NTM-PD by developing a population pharmacokinetic model and to explore the optimal pharmacotherapy in patients with NTM-PD. For this study, all data were retrospectively collected. The amikacin pharmacokinetic properties were best described by a two-compartment model with first-order elimination. The estimated glomerular filtration rate and body weight were identified as significant covariates for clearance and the volume of distribution, respectively. A model-based simulation was conducted to explore the probability of reaching the target therapeutic range when various dose regimens were administered according to the body weight and renal function. The simulation results indicated that the amikacin dosage should be determined based on the body weight, and for patients who weigh over 70 kg, it is necessary to adjust the dose according to renal function. In conclusion, the optimal pharmacotherapy of amikacin for patients with NTM-PD was recommended based on the population pharmacokinetic model, which is expected to enable the personalization of drug therapy and improve the clinical outcomes of amikacin therapy.

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