Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Levetiracetam is currently being used to treat epilepsy in pregnant women. The plasma concentration of levetiracetam drops sharply during pregnancy, and the inability of pregnant women to maintain therapeutic concentrations can lead to seizures. This study aimed to predict the changes in fetal and maternal plasma exposure to levetiracetam during pregnancy and provide advice on dose adjustment. The physiology-based pharmacokinetics (PBPK) model was developed using PK-Sim and Mobi software, and validated following comparison of the observed plasma concentration and pharmacokinetic parameters. The levetiracetam PBPK model for mother and the fetus at various stages of pregnancy was successfully established and verified. Predictions indicated that the area under the steady-state concentration-time curve for levetiracetam decreased to 83, 62, and 67% of baseline values in the first, second, and third trimesters, respectively. Based on PBPK predictions, the recommended dose of levetiracetam is 1.2, 1.6, and 1.5 times the baseline dose in the first, second, and third trimesters, respectively, not exceeding 4000 mg/day in the third trimester due to fetal safety. The levetiracetam PBPK model for pregnancy was successfully developed and validated, and could provide alternative levetiracetam dosing regimens across the stages of pregnancy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejps.2022.106349 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Recent Advances in Bioanalytical Methods for Quantification and Pharmacokinetic Analyses of Antibody-Drug Conjugates.
AAPS J
September 2025
Clinical Pharmacology Laboratory, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 5A03, Bethesda, Maryland, 20892, USA.
Antibody-drug conjugates (ADCs) represent a rapidly expanding class of therapeutics, uniquely combining the specificity of monoclonal antibodies with the potency of cytotoxic small-molecule payloads. Due to their inherent structural complexity and heterogeneous composition, accurate characterization and quantification of ADCs pose significant bioanalytical challenges. This review discusses recent advancements in bioanalytical methodologies, including ligand binding assays (LBAs), liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based approaches, and emerging hybrid LBA-LC-MS/MS platforms.
View Article and Find Full Text PDFConcentration-dependent blood binding: assessing implications through physiologically based Pharmacokinetic modeling of tacrolimus as a case example.
J Pharmacokinet Pharmacodyn
September 2025
Centre for Applied Pharmacokinetic Research (CAPKR), University of Manchester, Manchester, UK.
Concentration-dependent binding to red blood cells is a characteristic of several drugs, complicating the understanding of how pathophysiological factors influence drug behavior. This study utilized user-friendly, physiologically-based pharmacokinetic (PBPK) models to compare concentration-dependent and independent blood-to-plasma drug concentration ratios (B/P), using tacrolimus as a case study. Two models were developed and validated for tacrolimus using clinical data from healthy volunteers; Model 1 accounted for saturable blood binding, and Model 2 used a constant B/P level.
View Article and Find Full Text PDFCommentary and Review on Prospective Prediction of Bioequivalence of Oral Dosage Forms using Compendial Dissolution Testing and PBPK Modeling.
AAPS J
September 2025
Pharmaceutical Science, Pfizer Worldwide Research and Development, 445 Eastern Point Road, Groton, Connecticut, 06340, USA.
A virtual bioequivalence (VBE) approach utilizing physiologically based pharmacokinetic (PBPK) modeling presents a compelling alternative for pharmaceutical industries. This method can significantly reduce the time and cost associated with clinical bioequivalence (BE) trials while minimizing the risk of detecting a type II error (a false negative), as well as a type I error (a false positive). Additionally, it aligns with ethical considerations by obviating the need to expose healthy volunteers to investigational drugs.
View Article and Find Full Text PDFThe Impact of Using Measured In Vitro Data to Develop Physiologically Based Pharmacokinetic Models of Dermal Absorption: An IVIVE Case Study.
AAPS J
September 2025
Certara Predictive Technologies, Certara, Sheffield, UK.
In vitro permeation testing (IVPT) is commonly used to assess dermal drug delivery, yet its utility can be challenged by high variability and the need for large sample sizes to achieve sufficient statistical power. Dermal physiologically based pharmacokinetic (PBPK) models provide a mechanistic approach to better interpret IVPT results and to extrapolate in vitro to in vivo. In the present work, a dermal PBPK model for caffeine was developed using a bottom-up approach with minimal parameter optimization.
View Article and Find Full Text PDFVirtual Hepatic and Plasma Exposures of Voriconazole Administered to Cytochrome P450 2C19 Poor Metabolizers Predicted by Simplified and Full Pharmacokinetic Modeling Systems: Possible Causal Factor for Hepatic Disorders Seen in a Japanese Database.
Biol Pharm Bull
August 2025
Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
The broad-spectrum antifungal agent voriconazole elicits different responses. Polymorphisms in cytochrome P450 (P450) 2C19 may partially explain this variability. This study generated virtual plasma/hepatic exposures to voriconazole in Japanese P450 2C19 poor metabolizers using both simplified and population-based full physiologically based pharmacokinetic (PBPK) modeling systems.
View Article and Find Full Text PDF