The purpose of this study was to investigate the effect of the concentration-dependent erythrocyte distribution of TAK-802, a potent acetylcholinesterase inhibitor, on rat pharmacokinetics. In an ascending oral dose study, the maximum plasma concentration (C ) of TAK-802 increased in a dose-dependent manner. The time to reach C decreased as the dose increased, whereas the total clearance was independent of the tested dose range. In this intravenous (i.v.) ascending dose study in rats, the apparent distribution volumes at steady state decreased, and the apparent terminal elimination rate constants increased with TAK-802 dose escalation. A marked concentration dependency was observed in an associated in vitro erythrocyte distribution study. The in vitro erythrocyte distribution study results and a relationship analysis between the plasma and blood concentrations of TAK-802 after i.v. dosing revealed that the characteristics of the erythrocyte distribution could be expressed by Langmuir's adsorption formula. The concentration-time profiles of TAK-802 in plasma and whole blood calculated using a nonlinear pharmacokinetic model incorporating the concentration-dependent erythrocyte distribution with optimized parameters fit well to the observed plasma and blood concentration profiles obtained from the i.v. ascending dose study. These results indicate that the concentration-dependent erythrocyte distribution plays a major role in the nonlinear pharmacokinetics of TAK-802 in rats. Copyright © 2016 John Wiley & Sons, Ltd.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/bdd.2029 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Carbapenems in the management of valproic acid overdose (MPT-01166-24 R1).
Br J Clin Pharmacol
January 2025
Departments of Medicine, Pediatrics, and Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.
Severe valproic acid (VPA) overdose is characterized by coma (sometimes with cerebral oedema), respiratory depression, hypotension and metabolic abnormalities. Traditional management of VPA poisoning has been limited to gastrointestinal decontamination, L-carnitine supplementation and, in severe cases, haemodialysis. Recently, interest has developed in the use of carbapenem antibiotics as an adjunctive therapy in patients with severe VPA poisoning.
View Article and Find Full Text PDFIntegrating the ADS Score with 24-Hour ASPECTS and red cell distribution width for enhanced prediction of stroke-associated pneumonia following intravenous thrombolysis: model development and internal validation.
Eur J Med Res
January 2025
Division of Radiology, Saraburi Hospital, Saraburi, Thailand.
Introduction: Stroke-associated pneumonia (SAP) is a major cause of mortality during the acute phase of stroke. The ADS score is widely used to predict SAP risk but does not include 24-h non-contrast computed tomography-Alberta Stroke Program Early CT Score (NCCT-ASPECTS) or red cell distribution width (RDW). We aim to evaluate the added prognostic value of incorporating 24-h NCCT-ASPECTS and RDW into the ADS score and to develop a novel prediction model for SAP following thrombolysis.
View Article and Find Full Text PDFEvaluation of Hematological Parameters as Markers for Subclinical Inflammation in Adults with Familial Mediterranean Fever.
Middle East J Dig Dis
October 2024
Department of Epidemiology, High Institute of Public Health, Alexandria University, Alexandria, Egypt.
Background: Repeated polyserositis, another name for familial Mediterranean fever (FMF), is an autoimmune disorder with an autosomal recessive nature primarily characterized by short-lived repeated periods of peritonitis, pleuritis, and arthritis, generally accompanied by fever.
Methods: Our participants were divided into two groups. Group I (patients): 100 individuals who were diagnosed as patients with FMF and were monitored.
Long-term fasting induces a remodelling of fatty acid composition in erythrocyte membranes.
Eur J Clin Invest
January 2025
Buchinger Wilhelmi Clinic, Überlingen, Germany.
Introduction: Long-term fasting (LF) activates an adaptative response to switch metabolic fuels from food glucose to lipids stored in adipose tissues. The increase in free fatty acid (FFA) oxidation during fasting triggers health benefits. We questioned if the changes in lipid metabolism during LF could affect lipids in cell membranes in humans.
View Article and Find Full Text PDFUnveiling the Prognostic Power of HRR in ICU-Admitted COPD Patients: A MIMIC-IV Database Study.
Int J Chron Obstruct Pulmon Dis
January 2025
Department of Respiratory and Critical Care Medicine, The Second People's Hospital of Meishan City, Meishan, Sichuan, 620500, People's Republic of China.
Objective: This study sought to examine the potential relationship between Hemoglobin/Red Cell Distribution Width Ratio (HRR) and the all-cause mortality risk in critically ill patients with chronic obstructive pulmonary disease (COPD).
Patients And Methods: In a retrospective analysis of the MIMIC-IV database, patients were divided into two groups based on a specific HRR threshold. Propensity score matching (PSM) was employed to address covariate imbalances.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!