TY - JOUR T1 - A Physiologically Based Pharmacokinetic Model for Predicting Diazepam Pharmacokinetics after Intravenous, Oral, Intranasal, and Rectal Applications. AU - Khalid,Sundus, AU - Rasool,Muhammad Fawad, AU - Imran,Imran, AU - Majeed,Abdul, AU - Saeed,Hamid, AU - Rehman,Anees Ur, AU - Ashraf,Waseem, AU - Ahmad,Tanveer, AU - Bin Jardan,Yousef A, AU - Alqahtani,Faleh, Y1 - 2021/09/15/ PY - 2021/08/18/received PY - 2021/09/07/revised PY - 2021/09/13/accepted PY - 2021/9/28/entrez PY - 2021/9/29/pubmed PY - 2021/9/29/medline KW - Simcyp® KW - diazepam KW - intranasal KW - pharmacokinetics KW - physiologically based pharmacokinetic (PBPK) KW - rectal KW - route of administration JF - Pharmaceutics JO - Pharmaceutics VL - 13 IS - 9 N2 - 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). SN - 1999-4923 UR - https://www.unboundmedicine.com/medline/citation/34575556/A_Physiologically_Based_Pharmacokinetic_Model_for_Predicting_Diazepam_Pharmacokinetics_after_Intravenous_Oral_Intranasal_and_Rectal_Applications_ DB - PRIME DP - Unbound Medicine ER -