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Related Concept Videos

Bioavailability: Overview01:17

Bioavailability: Overview

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Bioavailability refers to the proportion of an administered drug that reaches the systemic circulation in its active, unaltered form. It is a crucial pharmacokinetic parameter that determines the effectiveness of a drug in achieving its intended therapeutic outcomes. The route of administration significantly influences bioavailability, with intravenous administration achieving 100% bioavailability as the drug directly enters the bloodstream. In contrast, oral administration often results in...
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Bioavailability: Overview01:13

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Bioavailability refers to the proportion of an unaltered drug that, after administration, enters the systemic circulation and can be distributed to the desired action site. Factors such as gastrointestinal (GI) absorption and liver biotransformation influence the bioavailability of a drug when it is administered orally. When a drug is administered intravenously, it enters the systemic circulation directly; by definition, its bioavailability is assumed to be 100%. The bioavailability of an...
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Bioavailability: Influencing Factors01:22

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Bioavailability refers to the extent and rate at which a drug reaches systemic circulation in its active form. Extent refers to the amount of the drug that makes it into circulation, while rate is the speed at which it enters circulation. It is influenced by several factors critical for optimizing drug formulations, dosing regimens, and therapeutic outcomes.Physicochemical properties of drugs and formulationsThe solubility, stability, and dissolution rate of a drug significantly impact its...
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When a drug is taken orally, it undergoes a journey starting from the gastrointestinal (GI) tract, passing through the portal vein, reaching the liver, and finally entering the systemic circulation. This process involves the absorption of the drug across the GI tract. The liver is the primary site for metabolizing the drug, with some metabolism also occurring in the gut wall. This journey significantly reduces the quantity of the drug that reaches the systemic circulation, a phenomenon known as...
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Upon entering the systemic circulation, drugs can distribute into the interstitial and intracellular fluid of various tissue cells. This distribution is facilitated by the binding of drugs to different cellular components within tissues, which may lead to drug accumulation in specific areas. Drugs bound to tissue components serve as reservoirs that release free drugs back into the system, prolonging the drug's overall action. However, this accumulation can also result in local toxicity.
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Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry01:20

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Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...
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Steroid hormone bioavailability is controlled by the lymphatic system.

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Lymphatic endothelial cells (LECs) metabolize progesterone, impacting immune tolerance during pregnancy and cancer. These cells modify hormone levels and influence immune cell responses, suggesting a key role in immune regulation.

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Area of Science:

  • Endocrinology
  • Immunology
  • Cell Biology

Background:

  • Progesterone is crucial for immune tolerance in pregnancy.
  • Altered progesterone metabolism is linked to pregnancy complications and cancer.
  • Lymphatic endothelial cells (LECs) are involved in tumor immunity.

Purpose of the Study:

  • To investigate if human LECs modify progesterone bioavailability.
  • To understand the role of LECs in progesterone metabolism and immune modulation.

Main Methods:

  • Incubation of primary human LECs and mouse lymph nodes with progesterone.
  • Analysis of progesterone metabolism using thin layer chromatography and liquid chromatography-mass spectrometry.
  • Assessment of steroidogenic enzyme and receptor expression via Real-time PCR.
  • Flow cytometry analysis of immune cell responses to progesterone metabolites.

Main Results:

  • LECs metabolize progesterone to 6α-OH-pregnanolone and can reactivate progesterone from precursors.
  • LECs express 17β-hydroxysteroid dehydrogenase 2, exhibiting antiandrogenic and antiestrogenic activity.
  • Progesterone and its metabolites reduce TNF-α and IFN-γ production in CD4+ and CD8+ T cells.

Conclusions:

  • Human LECs actively metabolize progesterone, influencing its bioavailability.
  • LECs are targets of steroid hormones and express relevant receptors and enzymes.
  • LECs play a significant immunomodulatory role in pregnancy and cancer through progesterone metabolism.