Formulation Strategies to Optimize Drug Pharmacokinetics and Improve Therapeutic Outcomes

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmacokinetics and Pharmacodynamics".

Deadline for manuscript submissions: closed (10 June 2024) | Viewed by 1482

Special Issue Editor

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Guest Editor
Samuel J. and Joan B. Williamson Institute for Pharmacometrics, Division of Pharmaceutical Sciences, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201, USA
Interests: pharmacokinetics; pharmacodynamics; PBPK modeling; drug–drug interactions; special populations
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Special Issue Information

Dear Colleagues,

Safe and effective drug therapy involves delivering the correct amount of medication over an appropriate timeframe so that target plasma concentrations are achieved and/or maintained. Pharmacokinetics is a critical determinant of drug action in vivo since it drives the systemic exposure that is achieved following drug administration. Undesirable pharmacokinetic properties can compromise drug safety and efficacy in various ways. For example, a medication with a short elimination half-life may require dosing a patient multiple times each day, which can negatively impact patient adherence. Additionally, wide fluctuations in plasma levels during a dosing interval can result in adverse effects resulting from high peak concentrations or loss of activity due to low trough levels of the drug. In these situations, and others, formulation scientists can develop novel delivery systems to improve the plasma profile of a medication, thereby optimizing therapeutic outcomes.

This issue is dedicated to investigations demonstrating the application of formulation science to improve pharmacokinetic profiles by modifying drug absorption, distribution, metabolism, or excretion. Pharmaceutical scientists are invited to share their research demonstrating how pharmacokinetic properties of a drug product were optimized through formulation development to improve bioavailability, reduce food effects, mitigate drug–drug interactions, provide patient-friendly dosing schedules, increase the safety profile of medication, etc.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: the development and in vivo characterization of modified release formulations; novel delivery systems for extravascular administration, including nasal and pulmonary routes; and applications of model-informed formulation development approaches, including physiologically based biopharmaceutics modeling (PBBM).

I look forward to receiving your contributions.

Prof. Dr. David R. Taft
Guest Editor

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  • formulation development
  • pharmacokinetics
  • biopharmaceutics
  • in vitro/in vivo extrapolation/correlation
  • bioavailability
  • modified release

Published Papers (1 paper)

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29 pages, 3835 KiB  
Simultaneously Predicting the Pharmacokinetics of CES1-Metabolized Drugs and Their Metabolites Using Physiologically Based Pharmacokinetic Model in Cirrhosis Subjects
by Xin Luo, Zexin Zhang, Ruijing Mu, Guangyu Hu, Li Liu and Xiaodong Liu
Pharmaceutics 2024, 16(2), 234; - 5 Feb 2024
Viewed by 1091
Hepatic carboxylesterase 1 (CES1) metabolizes numerous prodrugs into active ingredients or direct-acting drugs into inactive metabolites. We aimed to develop a semi-physiologically based pharmacokinetic (semi-PBPK) model to simultaneously predict the pharmacokinetics of CES1 substrates and their active metabolites in liver cirrhosis (LC) patients. [...] Read more.
Hepatic carboxylesterase 1 (CES1) metabolizes numerous prodrugs into active ingredients or direct-acting drugs into inactive metabolites. We aimed to develop a semi-physiologically based pharmacokinetic (semi-PBPK) model to simultaneously predict the pharmacokinetics of CES1 substrates and their active metabolites in liver cirrhosis (LC) patients. Six prodrugs (enalapril, benazepril, cilazapril, temocapril, perindopril and oseltamivir) and three direct-acting drugs (flumazenil, pethidine and remimazolam) were selected. Parameters such as organ blood flows, plasma-binding protein concentrations, functional liver volume, hepatic enzymatic activity, glomerular filtration rate (GFR) and gastrointestinal transit rate were integrated into the simulation. The pharmacokinetic profiles of these drugs and their active metabolites were simulated for 1000 virtual individuals. The developed semi-PBPK model, after validation in healthy individuals, was extrapolated to LC patients. Most of the observations fell within the 5th and 95th percentiles of simulations from 1000 virtual patients. The estimated AUC and Cmax were within 0.5–2-fold of the observed values. The sensitivity analysis showed that the decreased plasma exposure of active metabolites due to the decreased CES1 was partly attenuated by the decreased GFR. Conclusion: The developed PBPK model successfully predicted the pharmacokinetics of CES1 substrates and their metabolites in healthy individuals and LC patients, facilitating tailored dosing of CES1 substrates in LC patients. Full article
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