Modelling of neutrophil dynamics in children receiving busulfan or treosulfan for haematopoietic stem cell transplant conditioning

Abstract

Running title: Pharmacometric analysis of neutrophils in children receiving HSCT.

Can Published Population Pharmacokinetic Models of Busulfan Be Used for Individualized Dosing in Chinese Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation? An External Evaluation

“…41 Five of 11 popPK models (models F, H, G, I, K) incorporated both body size and maturation as covariates of CL. 12,[17][18][19][20] Model I employed IBW as an indicator of body size, which is usually used in the obese population. However, there are fewer obese Chinese patients compared to the White population.…”

“…Eleven studies were included according to the inclusion and exclusion criteria. 12,[14][15][16][17][18][19][20][21][22][23] The studies were conducted in the United States, Britain, Germany, France, Australia, Canada, Korea, and Japan, with 5 multiple-center studies and 6 single-center studies. Among the 11 studies, only 2 popPK models 16,19 (model E and model H) were developed in Asian.…”

“…Box plots of relative prediction error (PE%) for 11 published population pharmacokinetic models. 12,[14][15][16][17][18][19][20][21][22][23] Black solid line, red and blue dotted lines are reference lines indicating PE% of 0%, ±20%, and ±30%, respectively.…”

“…13 At present, there have been many studies describing population pharmacokinetic (popPK) models of busulfan. 12,[14][15][16][17][18][19][20][21][22][23] Personalized dosing therapies are increasingly using first dose recommendations and dose adjustments through popPK models. In the routine therapeutic drug monitoring of busulfan, many centers use popPK models to determine the dosing regimen, and dosage adjustment is performed based on Bayesian forecasting with limit concentration to ensure target AUC achievement.…”

“…Figure 3. Box plots relative individual prediction error with Bayesian forecasting for 11 published population pharmacokinetic models12,[14][15][16][17][18][19][20][21][22][23] in different scenarios (0 represents prediction without prior information and 1-3 represents with prior 1-3 observations, respectively). In scenario n, prior n observations were used to estimate the individual prediction and it was then compared with the corresponding observation.…”