External validation and updating of the infusion rate individualization of soybean oil-based intravenous lipid emulsion: A descriptive cohort study.

BACKGROUND: Safe and efficient provision of intravenous lipid emulsion (ILE) requires a strategy to individualize infusion rates. Estimating the maximum acceptable infusion rate (MaxInfRate) of soybean oil-based ILE (SO-ILE) in individuals by using a triglyceride (TG) kinetic model was reported to be feasible. In this study, we aimed to externally validate and, if needed, update the MaxInfRate estimation. METHODS: The maximum TG concentration (TGmax) in patients receiving SO-ILE at MaxInfRate was evaluated to determine if it met the definition of being <400 mg/dl for 90th percentile of patients. The TG kinetic model was evaluated through prediction performance checks and was subsequently updated using the data set of both the previous model development and present validation studies. RESULTS: Out of 83 patients, 74 had TGmax <400 mg/dl, corresponding to a probability of 89.2% (95% CI, 81.9%-95.2%), and the 90th percentile of TGmax was 400 mg/dl (95% CI, 328-490 mg/dl), closely aligned with the theoretical values. However, the individual TGmax values were biased by the infusion rate because the covariate effects were overestimated in the TG kinetic model, requiring a minor revision. The updated MaxInfRate with the combined data set showed unbiased and more accurate predictions. CONCLUSION: The MaxInfRate was validated in external inpatients and updated with all available data. MaxInfRate estimation for individuals could be an option for the safe and efficient provision of SO-ILE.

Individualization of the infusion rate of a soybean oil-based intravenous lipid emulsion for inpatients, based on baseline triglyceride concentrations: A population pharmacokinetic approach.

BACKGROUND: A rapid infusion rate for intravenous lipid emulsion (ILE) can cause adverse effects; therefore, safe and efficient infusion rates are desired. This study aimed to develop a triglyceride (TG) kinetic model after soybean oil-based ILE (SO-ILE) administration and individualize the infusion rate via a population pharmacokinetic approach. METHODS: Eighty-three inpatients were enrolled in this prospective observational study. A TG kinetic model was applied to the observations based on population pharmacokinetics using a nonlinear mixed-effect model. The patients' characteristics and laboratory parameters were evaluated to identify predictors of TG kinetics, and the maximum acceptable infusion rate was defined as that for which the maximum TG concentration did not exceed 400 mg/dl in 90% of patients. RESULTS: No adverse events associated with SO-ILE administration were observed. The developed TG kinetic model explained the observed TG concentrations and identified the baseline TG concentration and body weight as predictors of TG kinetics. The estimated maximum acceptable infusion rates greatly varied among individuals, ranging from <0.01 to 0.3 g/kg/h. CONCLUSION: The present study suggested the necessity and demonstrated the feasibility of individualizing the infusion rates of SO-ILE, using a population pharmacokinetic approach.