TY - GEN
T1 - 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
AU - Hasril, M.
AU - Luthfy, M.
AU - Riana, A.
AU - Ittaqa, A. N.
AU - Pawiro, S. A.
AU - Hardiansyah, D.
N1 - Funding Information:
This work was supported by the Department of Medical Physics and Biophysics, University of Indonesia (Hibah PUTI Prosiding 2020, Grant Number: NKB-986/UN2.RST/HKP.05.00/2020) for this research and publication. The authors thank the supervisor who has provided guidance and support for the completion of this study.
Publisher Copyright:
© 2021 Author(s).
PY - 2021/3/29
Y1 - 2021/3/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85103724750&partnerID=8YFLogxK
U2 - 10.1063/5.0047911
DO - 10.1063/5.0047911
M3 - Conference contribution
AN - SCOPUS:85103724750
T3 - AIP Conference Proceedings
BT - Proceedings of the International Conference and School on Physics in Medicine and Biosystem, ICSPMB 2020
A2 - Lubis, Lukmanda Evan
A2 - Nuzulia, Nur Aisyah
A2 - Hidayati, Nur Rahmah
PB - American Institute of Physics Inc.
T2 - 2020 International Conference and School on Physics in Medicine and Biosystem: Physics Contribution in Medicine and Biomedical Applications, ICSPMB 2020
Y2 - 6 November 2020 through 8 November 2020
ER -