Prediction of Drug Clearance in Preterm and Term Neonates by Minimal Physiologically Based Pharmacokinetic Model and Allometry: A Comparison with Whole BODY Physiologically Based Pharmacokinetic Model

Main Article Content

Iftekhar Mahmood, PhD

Abstract

Objectives: The objective of this study is to compare the predictive performance of a minimal physiologically based Pharmacokinetic model (mPBPK) and an allometric model with a whole body physiologically based pharmacokinetic Model (PBPK) to predict clearance of drugs in preterm and term neonates.


Methods: From the literature, 6 studies were identified in which clearance of drugs in preterm and term neonates were predicted by whole body PBPK model. The mPBPK model consisted of four physiological parameters; liver and kidney weights and blood flow to these organs. From allometric models, the values of these physiological parameters were predicted in the neonates. The sum of these four physiological parameters were then used to predict CL in the neonates using adult CL values. The allometric model was based on Age Dependent Exponent Model (ADE). ADE uses different allometric exponents across the age groups. These exponents are 1.2 for preterm and 1.1 for term neonates for age 0-3 months, exponents 1.0, 0.90, and 0.75 for >3 months-2 years, >2-5 years, and >5 years, respectively. For the prediction of CL in the neonates from allometry adult CL values were used. The predicted clearance values using PBPK and mPBPK and ADE model were compared with the experimental (clinical) values. The acceptable prediction error was within 0.5-1.5-fold.


Results: There were 26 drugs with 86 observations. From PBPK, mPBPK, and allometric models, 90.7%, 98.8%, and 93.0% observations were within 2-fold prediction error, respectively. From PBPK, mPBPK, and allometric models, 81.4%, 90.7%, and 84.9% observations were within 0.5-2-fold prediction error, respectively.


Conclusions: This study indicates that the predictive performance of whole body PBPK, mPBPK and allometric models are essentially similar for the prediction of drug clearance in preterm and term neonates. mPBPK and allometry are much easier to develop than whole body PBPK and are as accurate and robust as whole body PBPK.

Keywords: Preterm and term neonates, whole body PBPK model, minimal PBPK model, allometry, clearance

Article Details

How to Cite
MAHMOOD, Iftekhar. Prediction of Drug Clearance in Preterm and Term Neonates by Minimal Physiologically Based Pharmacokinetic Model and Allometry: A Comparison with Whole BODY Physiologically Based Pharmacokinetic Model. Medical Research Archives, [S.l.], v. 11, n. 8, aug. 2023. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/4315>. Date accessed: 13 july 2024. doi: https://doi.org/10.18103/mra.v11i8.4315.
Section
Research Articles

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