One size does not fit all: getting drug doses right for children

Hawcutt, Daniel B; Smyth, Rosalind L

doi:10.1136/adc.2007.127951

Cited by 7 publications

(3 citation statements)

References 7 publications

(8 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, the dosage ratios to adults based on BSA were between 1.09 and 1.10, almost the same as those of adults in this study. It was reported that although scaling methods based on BSA can be considered to overpredict clearance in neonates and infants after 6 months of age, BSA is a good marker as a basis of drug dosing 11,19 ; our results are consistent with those findings.…”

Section: Discussionsupporting

confidence: 94%

Comparison of Approved Dosages for Pediatric and Adult Populations Based on US Labeling Information

Hanada

Kaneko

Narukawa

2015

Ther Innov Regul Sci

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 94%

Comparison of Approved Dosages for Pediatric and Adult Populations Based on US Labeling Information

Hanada

Kaneko

Narukawa

2015

Ther Innov Regul Sci

View full text Add to dashboard Cite

show abstract

“…Our previous study showed that tripegfilgrastim 100 μg/kg reduced Grade 4 neutropenia and was generally tolerable in pediatric patients 19 . Although weight‐based dosing is frequently used, it has some disadvantages because of the inconvenience of administration and the nonlinear relationship between weight and dose 45,46 . Our simulation suggested that five weight‐tiered fixed doses of tripegfilgrastim achieved a similar reduction in Grade 4 neutropenia duration compared with weight‐based G‐CSF treatment with 100 μg/kg.…”

Section: Discussionmentioning

confidence: 74%

“… 19 Although weight‐based dosing is frequently used, it has some disadvantages because of the inconvenience of administration and the nonlinear relationship between weight and dose. 45 , 46 Our simulation suggested that five weight‐tiered fixed doses of tripegfilgrastim achieved a similar reduction in Grade 4 neutropenia duration compared with weight‐based G‐CSF treatment with 100 μg/kg. The median duration of Grade 4 neutropenia ranged from 6.3 to 7 days in the weight‐tiered fixed‐dose group, and the corresponding value was 6.5–7.2 days in the weight‐based dose group (Figure 5 ).…”

Section: Discussionmentioning

confidence: 76%

Semimechanistic pharmacokinetic–pharmacodynamic model of tripegfilgrastim for pediatric patients after chemotherapy

Lee

Hong

Jang

et al. 2023

CPT Pharmacom & Syst Pharma

View full text Add to dashboard Cite

Tripegfilgrastim is a long‐acting granulocyte colony‐stimulating factor (G‐CSF) that has been used to prevent chemotherapy‐induced neutropenia in adults. This study aimed to establish a pharmacokinetic (PK)–pharmacodynamic (PD) model to explore the impact of chemotherapy and tripegfilgrastim on absolute neutrophil counts (ANCs) and to further propose a fixed‐dose regimen in pediatric patients. Because neutrophils affect the clearance of tripegfilgrastim, the semimechanistic PK‐PD model was developed simultaneously by using data from 40 healthy adults and 27 pediatric patients with solid tumors. Tripegfilgrastim PK and ANC dynamics were described with a pharmacodynamics‐mediated drug disposition model assuming quasi‐equilibrium with five transit compartments mimicking neutrophil granulopoiesis. The effect of chemotherapy on neutrophils was included by stimulating the elimination of the G‐CSF receptor at the mitotic cells. Healthy adult and pediatric patients showed significantly different value for dissociation constant of the tripegfilgrastim‐G‐CSF receptor complex (Kd) and apparent volume of distribution (Vd/F). Patients treated with chemotherapy had a higher Vd/F and 62% lower Kd than healthy adults. As the age increased, the absorption rate of tripegfilgrastim was decreased. Body weight affected the G‐CSF receptor‐mediated internalization of tripegfilgrastim, and the baseline ANC value impacted the production rate of G‐CSF receptors. Simulations from the developed model suggested that 1.5, 2.5, 4, and 6 mg single subcutaneous tripegfilgrastim doses for the respective weight groups of 10–20, 21–30, 31–44, and more than 45 kg significantly reduced the duration of Grade 4 neutropenia similar to tripegfilgrastim weight‐based treatment with 100 μg/kg.

show abstract