Real-world cardiovascular effects of liraglutide: transportability analysis of the LEADER trial

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Hepatic Drug Clearance: Role of Transporters01:14

Hepatic Drug Clearance: Role of Transporters

In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...
115
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance01:07

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
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Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
438
Hepatic Drug Clearance: Effect of Protein Binding01:09

Hepatic Drug Clearance: Effect of Protein Binding

Hepatic clearance is influenced by protein binding based on the drug's extraction ratio. Drugs with high extraction ratios are considered flow-limited and remain unaffected by protein binding during hepatic clearance. On the other hand, drugs with low extraction ratios may be impacted by plasma protein binding, although the extent of this influence depends on the fraction of the drug bound.
For low-extraction-ratio drugs that are less than 80% protein-bound, minor changes in protein binding...
301
Nonlinear Pharmacokinetics: Role of Transporters01:27

Nonlinear Pharmacokinetics: Role of Transporters

A drug's nonlinear kinetics can be influenced by a diverse range of transporter proteins that serve as crucial players in drug distribution. These transporters, found within cells, can enhance or reduce local drug concentrations by facilitating the influx or efflux of drugs. For instance, the expression of xenobiotic transporters can be influenced by factors such as age and gender, potentially impacting the linearity of drug response.
Polymorphisms occurring in drug transporters can alter...
102
Non-Oral Extravascular Drug Absorption Routes01:15

Non-Oral Extravascular Drug Absorption Routes

Non-oral extravascular routes, which encompass sublingual, buccal, topical, intramuscular, and inhalation methods, primarily utilize passive diffusion to transport drugs into the systemic circulation. The absorption rates and effectiveness of these routes depend on the drug's physicochemical properties, as well as the patient's anatomical and pathophysiological state.
Lipophilic drugs that are stable at salivary pH (6) and exhibit minimal binding to the oral mucosa are absorbed more...
306