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Factors Influencing Drug Absorption: Presystemic Elimination

Factors Influencing Drug Absorption: Presystemic Elimination

The pharmacokinetic journey of oral drugs begins with a crucial first pass through the hepatic portal system, called the first-pass effect. This first pass significantly impacts bioavailability — the proportion of a drug that enters systemic circulation and is available for therapeutic action. The primary route sees the drug absorbed by intestinal membranes and then shunted to the liver via the hepatic portal vein. Here, pre-systemic elimination occurs as drugs face metabolism or biliary...

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Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport

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Related Experiment Video

Updated: Jul 18, 2026

Vein Interposition Model: A Suitable Model to Study Bypass Graft Patency

Vein Interposition Model: A Suitable Model to Study Bypass Graft Patency

Published on: January 15, 2017

Basic aspects of bypassing agents.

C Negrier¹, Y Dargaud, J C Bordet

¹Unité d'Hémostase Clinique, Centre Régional de Traitement de l'Hémophilie, Lyon, France. claude.negrier@chu-lyon.fr

Haemophilia : the Official Journal of the World Federation of Hemophilia

|November 25, 2006

Summary

Bypassing agents like activated prothrombin complex concentrates (aPCC) and recombinant factor VIIa (rFVIIa) aid in controlling bleeding. Their precise mechanisms, especially in complex coagulation pathways, require further research for improved clinical application.

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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers

Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers

Published on: October 17, 2013

Area of Science:

Hemostasis and Thrombosis
Pharmacology
Biochemistry

Background:

Bypassing agents, including activated prothrombin complex concentrates (aPCC) and recombinant factor VIIa (rFVIIa), are crucial for managing bleeding in hemophiliacs with inhibitors.
New indications for rFVIIa, such as in trauma and cerebral bleeds, are being explored in clinical trials.
The exact mechanisms of action for these hemostatic agents are not fully elucidated.

Purpose of the Study:

To review and clarify the mechanisms of action of aPCC and rFVIIa in hemostasis.
To highlight recent advancements in understanding their procoagulant effects.
To identify areas needing further investigation, including cellular interactions and monitoring techniques.

Main Methods:

Review of in vitro and animal model studies demonstrating the roles of activated factor X and prothrombin in aPCC activity.
Analysis of studies investigating both tissue factor-dependent and -independent pathways for rFVIIa.
Examination of research on cellular surface interactions, particularly platelet membrane involvement in coagulation complex formation.
Assessment of progress in understanding fibrin formation kinetics and ex vivo monitoring methods.

Main Results:

aPCC's hemostatic effect involves contributions from activated factor X and prothrombin.
rFVIIa enhances coagulation via complex tissue factor-dependent and -independent pathways.
Cellular surfaces, especially platelets, play a key role in Xase complex and thrombin generation.
Significant progress has been made in the last decade in understanding these agents' effects on coagulation.

Conclusions:

The mechanisms underlying the efficacy of aPCC and rFVIIa are multifaceted and involve complex interactions at cellular levels.
Further research is needed to fully understand their impact on fibrin formation kinetics.
Standardized ex vivo monitoring methods for assessing in vivo hemostasis remain a challenge.