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A Physiologically Based Pharmacokinetic Model for Predicting Diazepam Pharmacokinetics after Intravenous, Oral, Intranasal, and Rectal Applications

Khalid, Sundus, Rasool, Muhammad Fawad, Imran, Imran, Majeed, Abdul, Saeed, Hamid, Rehman, Anees ur, Ashraf, Waseem, Ahmad, Tanveer, Bin Jardan, Yousef A., Alqahtani, Faleh·2021·Pharmaceutics
DOI 10.3390/pharmaceutics13091480
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Abstract

Diazepam is one of the most prescribed anxiolytic and anticonvulsant that is administered through intravenous (IV), oral, intramuscular, intranasal, and rectal routes. To facilitate the clinical use of diazepam, there is a need to develop formulations that are convenient to administer in ambulatory settings. The present study aimed to develop and evaluate a physiologically based pharmacokinetic (PBPK) model for diazepam that is capable of predicting its pharmacokinetics (PK) after IV, oral, intranasal, and rectal applications using a whole-body population-based PBPK simulator, Simcyp®. The model evaluation was carried out using visual predictive checks, observed/predicted ratios (Robs/pred), and the average fold error (AFE) of PK parameters. The Diazepam PBPK model successfully predicted diazepam PK in an adult population after doses were administered through IV, oral, intranasal, and rectal routes, as the Robs/pred of all PK parameters were within a two-fold error range. The developed model can be used for the development and optimization of novel diazepam dosage forms, and it can be extended to simulate drug response in situations where no clinical data are available (healthy and disease).

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Cited by

Metadata

Authors
Khalid, S., Rasool, M. F., Imran, I., Majeed, A., Saeed, H., Rehman, A. U., Ashraf, W., Ahmad, T., Bin Jardan, Y. A., & Alqahtani, F.
Venue
Pharmaceutics
Publisher
MDPI AG
Published
2021-09-15
Volume
13
Issue
9
Pages
1480
ISSN
1999-4923
DOI
10.3390/pharmaceutics13091480
Cited by
17
References
4
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
Distinguished Scientist Fellowship program at King Saud University (RSP-2021/131)

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