Study the effect of the physiological parameters to the optimal administration of lysine/arginine during peptide receptor radionuclide therapy (PPRT) using a physiologically-based pharmacokinetic (PBPK) model

M. Hasril, M. Luthfy, A. Riana, A. N. Ittaqa, S. A. Pawiro, D. Hardiansyah

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

Abstract

This study aimed to determine the effect of the physiological parameters (PP) to the optimal administration of Lysine/Arginine for kidney protection during peptide-receptor radionuclide therapy (PRRT) using the Physiologically-based Pharmacokinetic (PBPK) model. Modeling of PBPK was performed to describe the bio-distribution of Lysine/Arginine in three patients of Neuroendocrine Tumor. The fitted PBPK model to the bio-distribution of Lysine/Arginine recently reported in the literature was used as the basic framework for the study's analysis in this study. The investigated PPs were blood flow out of the organ to the veins (Fout), organ clearance (c), and the total number of kidneys receptor (RK). Simulations were performed to investigate the effect of the PPs to the optimal time of 90Y-DOTATATE injection (TI), the Lysine/Arginine dose (DO), and the duration of the administered Lysine/Arginine dose (DU). In these simulations, each PP was varied to the ±SD, ±25%, ±50%, and ±75% of the mean values. The optimal values of TI, DO, and DU were determined based on the smallest AUC (Area Under the Curve) of the peptide in the proximal tubule of the kidneys organ (The smallest AUC value indicates the smallest dose). As a result, the optimal TI, DO, and DU was 31 min, 50 gr Lysine and 50 gr Arginine, and 180 min, respectively. We found that the PPs have a marginal effect on the determination of the optimal administration of the Lysine/Arginine except for the organ clearance (c) parameter which gives a significant change in the AUC value (coefficients of variation CV up to 58.32%, 95%, and 65.54 for TI, DO, and DU, respectively). According to our three patient's model, the currently-used peptide injection at minute 31 (average from three patients) after amino acid infusion and distribution of the 50 gr Lysine and 50 gr Arginine which administered over 180 minutes was suitable for clinical use. Additionally, organ clearance (c) was the most critical parameter on the bio-distribution of Lysine/Arginine.

Original languageEnglish
Title of host publicationProceedings of the International Conference and School on Physics in Medicine and Biosystem, ICSPMB 2020
Subtitle of host publicationPhysics Contribution in Medicine and Biomedical Applications
EditorsLukmanda Evan Lubis, Nur Aisyah Nuzulia, Nur Rahmah Hidayati
PublisherAmerican Institute of Physics Inc.
ISBN (Electronic)9780735440876
DOIs
Publication statusPublished - 29 Mar 2021
Event2020 International Conference and School on Physics in Medicine and Biosystem: Physics Contribution in Medicine and Biomedical Applications, ICSPMB 2020 - Depok, Virtual, Indonesia
Duration: 6 Nov 20208 Nov 2020

Publication series

NameAIP Conference Proceedings
Volume2346
ISSN (Print)0094-243X
ISSN (Electronic)1551-7616

Conference

Conference2020 International Conference and School on Physics in Medicine and Biosystem: Physics Contribution in Medicine and Biomedical Applications, ICSPMB 2020
CountryIndonesia
CityDepok, Virtual
Period6/11/208/11/20

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