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Quantitatively Predicting Effects of Exercise on Pharmacokinetics of Drugs Using a Physiologically Based Pharmacokinetic Model.
Drug Metab Dispos
October 2024
Department of Pharmacology, China Pharmaceutical University, Nanjing, China
Article Synopsis
- Exercise impacts various physiological functions, including increases in cardiac output and muscle blood flow, while decreasing glomerular filtration rate and liver blood flow, affecting how drugs are absorbed, distributed, metabolized, and excreted.
- The study developed a database of these changes during exercise and created equations to connect different physiological parameters with exercise intensity, using heart rate as a key index.
- The whole-body physiologically based pharmacokinetic (WB-PBPK) model demonstrated that drug concentrations during exercise could be predicted, showing significant effects of exercise conditions on drug pharmacokinetics based on sensitivity analysis.
Physiologically-based pharmacokinetic modeling of quinidine to establish a CYP3A4, P-gp, and CYP2D6 drug-drug-gene interaction network.
CPT Pharmacometrics Syst Pharmacol
August 2023
Clinical Pharmacy, Saarland University, Saarbrücken, Germany.
Article Synopsis
- Quinidine is an antiarrhythmic drug that inhibits CYP2D6 and P-glycoprotein, making it important for studying drug-drug interactions (DDIs), but it's also affected by interactions with CYP3A4 and P-gp since it's a substrate of these proteins.
- A physiologically-based pharmacokinetic (PBPK) model of quinidine was developed to analyze how it absorbs, distributes, metabolizes, and is excreted in the body, also involving its metabolite, 3-hydroxyquinidine.
- The model demonstrated high accuracy, successfully simulating complex DDI scenarios with over 90% of predicted outcomes aligning closely with actual clinical data, and it will be made
Optimization of dose and route of administration of the P-glycoprotein inhibitor, valspodar (PSC-833) and the P-glycoprotein and breast cancer resistance protein dual-inhibitor, elacridar (GF120918) as dual infusion in rats.
Pharmacol Res Perspect
April 2021
Biogen Inc, Cambridge, MA, USA.
Transporters can play a key role in the absorption, distribution, metabolism, and excretion of drugs. Understanding these contributions early in drug discovery allows for more accurate projection of the clinical pharmacokinetics. One method to assess the impact of transporters in vivo involves co-dosing specific inhibitors.
View Article and Find Full Text PDFComparative pharmacokinetic profile of cimicoxib in dogs and cats after IV administration.
Vet J
April 2021
Scientific Division of Vetoquinol, 70200 Lure, France.
Cimicoxib is a selective COX-2 inhibitor (coxib) registered for the treatment of pain and inflammation in dogs. Pharmacokinetics of some coxibs have been described in dogs and cats. In cats, total body clearance values are lower and terminal half-lives of the coxibs are longer than those in dogs.
View Article and Find Full Text PDFOrganic Cation Transporter 1 and 3 Contribute to the High Accumulation of Dehydrocorydaline in the Heart.
Drug Metab Dispos
October 2020
Laboratory of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
Dehydrocorydaline (DHC), one of the main active components of , is an important remedy for the treatment of coronary heart disease. Our previous study revealed a higher unbound concentration of DHC in the heart than plasma of mice after oral administration of extract or DHC, but the underlying uptake mechanism remains unelucidated. In our investigations, we studied the transport mechanism of DHC in transgenic cells, primary neonatal rat cardiomyocytes, and animal experiments.
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