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 4000Â 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 |
Pharmaceutics
January 2025
Department of Pharmaceutical Bioscience, Translational Drug Discovery and Development, Uppsala University, SE-75124 Uppsala, Sweden.
: N-acetyl-galactosamine small interfering RNAs (GalNAc-siRNA) are an emerging class of drugs due to their durable knockdown of disease-related proteins. Direct conjugation of GalNAc onto the siRNA enables targeted uptake into hepatocytes via GalNAc recognition of the Asialoglycoprotein Receptor (ASGPR). With a transient plasma exposure combined with a prolonged liver half-life, GalNAc-siRNA exhibits distinct disposition characteristics.
View Article and Find Full Text PDFPharmaceutics
January 2025
Department of Pharmaceutical Science, School of Pharmacy and Nutrition, University of Navarra, 31009 Pamplona, Spain.
Background/objectives: Colorectal cancer (CRC) holds the third and second position among cancers affecting men and women, respectively. Frequently, the first-line treatment for metastatic CRC consists of the intravenous administration of 5-fluorouracil and leucovorin in combination with oxaliplatin or irinotecan. Physiologically-based pharmacokinetic models (PBPK) aim to mechanistically incorporate body physiology and drug physicochemical attributes, enabling the description of both systemic and organ drug exposure based on the treatment specificities.
View Article and Find Full Text PDFPharmaceutics
December 2024
PerMed Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal.
Background: Salbutamol, a short-acting β-agonist used in asthma treatment, is available in multiple formulations, including inhalers, nebulizers, oral tablets, and intravenous, intramuscular, and subcutaneous routes. Each formulation exhibits distinct pharmacokinetic (PK) and pharmacodynamic (PD) profiles, influencing therapeutic outcomes and adverse effects. Although asthma management predominantly relies on inhaled salbutamol, understanding how these formulations interact with patient-specific characteristics could improve personalized medicine approaches, potentially uncovering the therapeutic benefits of alternative formulations for an individual patient.
View Article and Find Full Text PDFArch Toxicol
January 2025
Scientist Emeritus, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Hexabromocyclododecane (HBCD) is a brominated flame retardant, that is added, but not chemically bonded, to consumer products. HBCD is sold as a commercial-grade HBCD mixture containing three major stereoisomers: alpha (α), beta (β), and gamma (γ), with relative amounts of 12% for α-HBCD, 6% for β-HBCD, and 82% for γ-HBCD. HBCDs are widely measured in the environment and in biological matrices.
View Article and Find Full Text PDFIntroduction: Tuberculosis (TB) poses a significant threat to global health, with millions of new infections and approximately one million deaths annually. Various modeling efforts have emerged, offering tailored data-driven and physiologically-based solutions for novel and historical compounds. However, this diverse modeling panorama may lack consistency, limiting result comparability.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!