First-pass Metabolism
First-pass Metabolism - Related Videos
01:12
First Pass Effect
0 Views •
2023
Presystemic elimination, or the first-pass effect, is the metabolism of drugs that reduces their effective concentration at the site of action. Apart from the first-pass effect, the systemic bioavailability of the drug is also reduced by other factors, including incomplete absorption or chemical degradation of drugs. Depending on the route of administration, drugs can be metabolized in the liver, intestine, lungs, and vasculature. Orally administered drugs are first absorbed through the...
05:41
Metabolic Profile Analysis of Zebrafish Embryos
0 Views •
Cited by 42 •
2013
Zebrafish represent a powerful vertebrate model that has been under-utilised for metabolic studies. Here we describe a rapid way to measure the in vivo metabolic profile of developing zebrafish that allows the comparison of different mitochondrial function parameters between genetically or pharmacologically manipulated embryos, thereby increasing the applicability of this organism.
01:25
Single-pass Transmembrane Proteins
0 Views •
2023
Integral membrane proteins are tightly associated with the cell membrane and play a crucial role in cell communication, signaling, adhesion, and transport of the molecules. Some integral membrane proteins are present only in the membrane monolayer. For example, the enzyme fatty acid amide hydrolase is present in the cytoplasmic side of the membrane monolayer. In contrast, another type of integral membrane protein, also known as a transmembrane protein, spans across the membrane. Transmembrane...
10:19
An Introduction to Cell Metabolism
0 Views •
2023
In cells, critical molecules are either built by joining together individual units like amino acids or nucleotides, or broken down into smaller components. Respectively, the reactions responsible for this are referred to as anabolic and catabolic. These reactions require or produce energy typically in the form of a “high-energy” molecule called ATP. Together, these processes make up “Cell Metabolism,” and are hallmarks of healthy, living cells.JoVE’s introduction to cell metabolism briefly...
01:23
Factors Influencing Bioavailability: First-Pass Elimination
0 Views •
2023
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...
FAQs
After absorption, drug molecules encounter enzymatic activity in both the intestinal wall and liver before systemic circulation. Cytochrome P450 proteins and conjugation systems chemically transform the molecules during this presystemic passage. Because these reactions occur before the drug is widely distributed, they can determine how much unchanged drug remains available to produce a pharmacologic effect.
First-pass reactions do not produce one uniform outcome. Depending on the drug and the enzymatic transformation, metabolites may be inactive, pharmacologically active, or toxic. This distinction matters in pharmacology because a reduction in unchanged drug concentration does not necessarily mean loss of all drug-related activity; the resulting metabolite can alter the overall therapeutic or adverse response.
Changing the administration route can reduce the impact of presystemic loss. Oral dosing exposes absorbed molecules to the intestinal wall and portal passage before they reach systemic circulation, whereas intravenous, sublingual, or transdermal delivery can provide alternatives to that pathway. Route selection therefore becomes important when oral exposure is insufficient for the intended response.
A medicine may require a higher oral dose when first-pass enzymes remove a substantial portion of the absorbed drug before systemic circulation. Dose selection must therefore account not only for absorption from the gastrointestinal tract but also for presystemic enzymatic breakdown. If this reduction is overlooked, circulating concentrations may be lower than needed for a therapeutic response.
A weak response after oral administration may reflect extensive presystemic breakdown rather than inadequate absorption alone. The amount reaching circulation, the activity of any metabolites, and the possibility of toxic products all influence the observed effect. Pharmacologists therefore connect oral dose, circulating concentration, and therapeutic response when evaluating how a medicine behaves.
An alternative route becomes relevant when presystemic metabolism is expected to reduce circulating drug concentrations enough to compromise the intended effect or complicate dose selection. The overview identifies intravenous, sublingual, and transdermal delivery as options. Choosing among them changes whether the drug follows the gastrointestinal, portal, and hepatic sequence associated with oral dosing.
Its interaction relevance follows from the enzymes that transform drugs before systemic circulation. If those enzymatic processes alter the amount of unchanged drug or the types of metabolites produced, circulating exposure and pharmacologic effects may change. Consequently, first-pass metabolism belongs in pharmacology assessments of interactions, therapeutic response, and the possibility of toxic or active metabolites.