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

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101534003 Publication Model: Electronic Cited Medium: Print ISSN: 1999-4923 (Print) Linking ISSN: 19994923 NLM ISO Abbreviation: Pharmaceutics Subsets: PubMed not MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI
    • 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 (R obs/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 R obs/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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    • Grant Information:
      RSP-2021/131 Distinguished Scientist Fellowship program at King Saud University
    • Contributed Indexing:
      Keywords: Simcyp®; diazepam; intranasal; pharmacokinetics; physiologically based pharmacokinetic (PBPK); rectal; route of administration
    • Publication Date:
      Date Created: 20210928 Latest Revision: 20211001
    • Publication Date:
      20231215
    • Accession Number:
      PMC8465253
    • Accession Number:
      10.3390/pharmaceutics13091480
    • Accession Number:
      34575556