(Updated: July 22, 2022)

3rd of December 2022

Kobe University "Program for fostering the next generation of outstanding
doctoral students through co-creation in different fields"
Prioritized Research Funds (2022) Application Form
1. Research Topics
Development of a physiologically based pharmacokinetic model of fentanyl for preventing central
toxicity in neonate patients on respiratory support

2. Applicant Information
Name: Walaa Yousef Bassyouni Mahdy
Affiliation: Department of Pharmaceutics, Graduate School of Medicine
Student number: 198M910M
Email address: w.you.med@gmail.com

3. Please provide information (between 500 to 1000 words) such as expenditure items, the
purpose of each item, amount of each item, expenditure period, and expected results pertaining to
the prioritized research funds. If there are multiple items, please provide information for each item.

[Expenditure item]
Simcyp Physiologically-based Pharmacokinetic Modeling (PBPK) software-related workshops, and
Journal submission.

[Purpose of expenditure]
Attending the workshops provided by Simcyp in order to obtain the information necessary to finish
our current study.

[Amount]
250,000 yen

[Expenditure period]
from December 2022 to September 2023

[Expected results]
Successfully acquiring necessary knowledge from these different workshops and incorporating it in
our current complicated work, and if I could not get the fund, attending these kinds of workshops
would be hard which eventually will affect my research.

[Other information (please describe any points freely)]

Simcyp is a software used to construct PBPK models, and it is one of the software programs released
by the UK-based Certara corporation, UK. Workshops offered by Ceratara help ensure that PBPK
models are developed effectively and accurately. These workshops covered a wide range of topics
on a variety of different levels. I received one of them (043 Simcyp Focused Workshop: Best Practice
in PBPK Model Building - February 21-25, 2022). The enhancement of PBPK model building strategy
was the primary focus of this one. I utilized a great deal of the information I gained from that workshop
in my previous article manuscript, which we submitted almost a month ago to the high impact journal
related to clinical pharmacology.
During the months of January and February 2023, they held more than six different workshops. And
I believe that participating in some of these workshops would be extremely beneficial to my present
and future work, as well as a significant step toward completing my Ph.D. dissertation.
The cost of these courses ranged between £1,100 and £4,200.
Our main focus is on pediatric population who took fentanyl (one of the powerful analgesic and
sedative) and susceptible to central toxicity. Fentanyl is widely used for sedation in preterm neonates
requiring artificial ventilation. Neonates are especially vulnerable to side effects such as respiratory
depression with oversedation which has a direct concentration-effect relation. The dosage regimen
is usually derived from adults employing an extrapolation based on body weight which cannot
accurately determine organ maturation in neonates. There is a necessity for model-based precision
 (Updated: July 22, 2022)

dosing of fentanyl that includes maturation. This study aimed to develop a pragmatic PBPK model
of fentanyl and evaluate its prediction accuracy in neonates. Thus, the goals of this study were to
design, validate, and personalize pediatric and preterm PBPK models. We also assessed the dose-
concentration-response relationship in 53 Japanese preterm patients admitted in the NICU at Kobe
University Hospital.
Using our PBPK model, we can further optimize fentanyl dosing regimens across pediatric and
preterm populations and further our understanding of the pharmacokinetics and toxicity of fentanyl
in these vulnerable populations. I have a substantial need of paid workshops for this highly
complicated modeling and simulation.

[Expenditure item]
Journal submission.

[Purpose of expenditure]
Journal submission fees.

[Amount]
250,000 yen

[Expenditure period]
from December 2022 to September 2023

[Expected results]
Publishing our present work in a prestigious Journal like Clinical and Translational Science, or CPT:
Pharmacometrics & Systems Pharmacology), and if I could not get the fund, publishing in these
kinds of journals would be challenging.

[Other information (please describe any points freely)]

It is an extremely time-consuming and expensive process to publish in a well-regarded open
access publication. We recently had a paper accepted for publication in the Clinical and
Translational Science journal. The paper is titled "PBPK Model to Investigate the Effect of
Pregnancy on Risperidone and Paliperidone Pharmacokinetics: Application to a Pregnant Woman
and her Neonate" (Impact factor: 4.689 2020, Journal Citation Reports (Clarivate Analytics):
55/140 (Medicine, Research & Experimental), Online ISSN: 1752-80. And we are currently working
on another paper with promising results. Of course, publishing another one in a highly regarded
publication would boost our department's or university's overall ranking, so we could use some
financial assistance.