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47-404: 57279 ENSG00000178537 ENSMUSG00000032602 O43772 Q9Z2Z6 NM_000387 NM_020520 NP_000378 NP_065266 Carnitine-acylcarnitine translocase (CACT) is responsible for passive transport of carnitine and carnitine - fatty acid complexes and across the inner mitochondrial membrane as part of the carnitine shuttle system . Fatty acyl–carnitine can diffuse from
94-433: A drug is an average value ; to take population variability into account, deviation range is shown as ± . To ensure that the drug taker who has poor absorption is dosed appropriately, the bottom value of the deviation range is employed to represent real bioavailability and to calculate the drug dose needed for the drug taker to achieve systemic concentrations similar to the intravenous formulation. To dose without knowing
141-413: A drug to reach C max . While the mechanisms by which a formulation affects bioavailability and bioequivalence have been extensively studied in drugs, formulation factors that influence bioavailability and bioequivalence in nutritional supplements are largely unknown. As a result, in nutritional sciences, relative bioavailability or bioequivalence is the most common measure of bioavailability, comparing
188-424: A drug, a pharmacokinetic study must be done to obtain a plasma drug concentration vs time plot for the drug after both intravenous (iv) and extravascular (non-intravenous, i.e., oral) administration. The absolute bioavailability is the dose-corrected area under curve ( AUC ) non-intravenous divided by AUC intravenous. The formula for calculating the absolute bioavailability, F , of a drug administered orally (po)
235-400: A less negative water potential will draw in water, but this depends on other factors as well such as solute potential (pressure in the cell e.g. solute molecules) and pressure potential (external pressure e.g. cell wall). There are three types of Osmosis solutions: the isotonic solution, hypotonic solution, and hypertonic solution. Isotonic solution is when the extracellular solute concentration
282-562: Is a stub . You can help Misplaced Pages by expanding it . Passive transport Passive transport is a type of membrane transport that does not require energy to move substances across cell membranes . Instead of using cellular energy , like active transport , passive transport relies on the second law of thermodynamics to drive the movement of substances across cell membranes. Fundamentally, substances follow Fick's first law , and move from an area of high concentration to an area of low concentration because this movement increases
329-400: Is a critical measurement used to assess the bioavailability differences from patient to patient in order to ensure predictable dosing. ^ TH: One of the few exceptions where a drug shows F of over 100% is theophylline . If administered as an oral solution F is 111%, since the drug is completely absorbed and first-pass metabolism in the lung after intravenous administration
376-405: Is absorbed. Bioavailability is a term used to describe the percentage of an administered dose of a xenobiotic that reaches the systemic circulation. It is denoted by the letter f (or, if expressed in percent, by F ). In nutritional science , which covers the intake of nutrients and non-drug dietary ingredients, the concept of bioavailability lacks the well-defined standards associated with
423-478: Is balanced with the concentration inside the cell. In the Isotonic solution, the water molecules still move between the solutions, but the rates are the same from both directions, thus the water movement is balanced between the inside of the cell as well as the outside of the cell. A hypotonic solution is when the solute concentration outside the cell is lower than the concentration inside the cell. In hypotonic solutions,
470-429: Is given below (where D is dose administered). Therefore, a drug given by the intravenous route will have an absolute bioavailability of 100% ( f = 1), whereas drugs given by other routes usually have an absolute bioavailability of less than one. If we compare the two different dosage forms having same active ingredients and compare the two drug bioavailability is called comparative bioavailability. Although knowing
517-463: Is lower due to intestinal epithelium absorption and first-pass metabolism . Thereby, mathematically, bioavailability equals the ratio of comparing the area under the plasma drug concentration curve versus time (AUC) for the extravascular formulation to the AUC for the intravascular formulation. AUC is used because AUC is proportional to the dose that has entered the systemic circulation. Bioavailability of
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#1733085162660564-526: Is measured by calculating the area under curve (AUC) of the drug concentration time profile. Bioavailability is the measure by which various substances in the environment may enter into living organisms. It is commonly a limiting factor in the production of crops (due to solubility limitation or absorption of plant nutrients to soil colloids) and in the removal of toxic substances from the food chain by microorganisms (due to sorption to or partitioning of otherwise degradable substances into inaccessible phases in
611-431: Is not required in order for molecules to pass through the cell membrane. Active transport of protons by H ATPases alters membrane potential allowing for facilitated passive transport of particular ions such as potassium down their charge gradient through high affinity transporters and channels. An example of facilitated diffusion is when glucose is absorbed into cells through Glucose transporter 2 (GLUT2) in
658-425: Is that facilitated diffusion requires a transport protein to 'facilitate' or assist the substance through the membrane. After a meal, the cell is signaled to move GLUT2 into membranes of the cells lining the intestines called enterocytes . With GLUT2 in place after a meal and the relative high concentration of glucose outside of these cells as compared to within them, the concentration gradient drives glucose across
705-436: Is the fraction of exposure to a drug (AUC) through non-intravenous administration compared with the corresponding intravenous administration of the same drug. The comparison must be dose normalized (e.g., account for different doses or varying weights of the subjects); consequently, the amount absorbed is corrected by dividing the corresponding dose administered. In pharmacology, in order to determine absolute bioavailability of
752-437: Is the necessity to conduct preclinical toxicity tests to ensure adequate safety, as well as potential problems due to solubility limitations. These limitations may be overcome, however, by administering a very low dose (typically a few micrograms) of an isotopically labelled drug concomitantly with a therapeutic non-isotopically labelled oral dose (the isotopically labelled intravenous dose is sufficiently low so as not to perturb
799-421: Is the net movement of material from an area of high concentration to an area with lower concentration. The difference of concentration between the two areas is often termed as the concentration gradient , and diffusion will continue until this gradient has been eliminated. Since diffusion moves materials from an area of higher concentration to an area of lower concentration, it is described as moving solutes "down
846-490: Is the passive movement of solute from a high concentration to a lower concentration until the concentration of the solute is uniform throughout and reaches equilibrium. Osmosis is much like simple diffusion but it specifically describes the movement of water (not the solute) across a selectively permeable membrane until there is an equal concentration of water and solute on both sides of the membrane. Simple diffusion and osmosis are both forms of passive transport and require none of
893-453: The cell membrane without any special membrane proteins. No energy is required because the movement of the gasses follows Fick's first law and the second law of thermodynamics . Facilitated diffusion, also called carrier-mediated osmosis, is the movement of molecules across the cell membrane via special transport proteins that are embedded in the plasma membrane by actively taking up or excluding ions . Through facilitated diffusion, energy
940-410: The entropy of the overall system . The rate of passive transport depends on the permeability of the cell membrane, which, in turn, depends on the organization and characteristics of the membrane lipids and proteins . The four main kinds of passive transport are simple diffusion , facilitated diffusion , filtration , and/or osmosis . Passive transport follows Fick's first law . Diffusion
987-425: The lungs and quickly diffuses across the membrane of alveoli and enters the circulatory system by diffusing across the membrane of the pulmonary capillaries. Simultaneously, carbon dioxide moves in the opposite direction, diffusing across the membrane of the capillaries and entering into the alveoli, where it can be exhaled. The process of moving oxygen into the cells, and carbon dioxide out, occurs because of
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#17330851626601034-407: The "average speed" is ∼ 2 d D / x {\displaystyle \sim 2dD/x} . This means that in the same physical environment, diffusion is fast when the distance is small, but less when the distance is large. This can be seen in material transport within the cell. Prokaryotes typically have small bodies, allowing diffusion to suffice for material transport within
1081-510: The bioavailability of one formulation of the same dietary ingredient to another. The absolute bioavailability of a drug, when administered by an extravascular route, is usually less than one (i.e., F < 100%). Various physiological factors reduce the availability of drugs prior to their entry into the systemic circulation. Whether a drug is taken with or without food will also affect absorption, other drugs taken concurrently may alter absorption and first-pass metabolism, intestinal motility alters
1128-440: The carnitine shuttle system from moving fatty acids across the mitochondrial membrane, leading to a decrease in fatty acid catabolism. The result is an accumulation of fatty acid within muscles and liver, decreased tolerance to long term exercise, inability to fast for more than a few hours, muscle weakness and wasting, and a strong acidic smell on the breath (due to protein catabolism). This membrane protein –related article
1175-457: The cell membrane through GLUT2. Filtration is movement of water and solute molecules across the cell membrane due to hydrostatic pressure generated by the cardiovascular system . Depending on the size of the membrane pores, only solutes of a certain size may pass through it. For example, the membrane pores of the Bowman's capsule in the kidneys are very small, and only albumins , the smallest of
1222-407: The cell to shrink. Bioavailability In pharmacology , bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation . By definition, when a medication is administered intravenously , its bioavailability is 100%. However, when a medication is administered via routes other than intravenous, its bioavailability
1269-533: The cell's ATP energy . For passive diffusion, the law of diffusion states that the mean squared displacement is ⟨ r 2 ⟩ = 2 d D t {\displaystyle \langle r^{2}\rangle =2dDt} with d being the number of dimensions and D the diffusion coefficient ). So to diffuse a distance of about x {\displaystyle x} takes time ∼ x 2 / 2 d D {\displaystyle \sim x^{2}/2dD} , and
1316-410: The cell. Larger cells like eukaryotes would either have very low metabolic rate to accommodate the slowness of diffusion, or invest in complex cellular machinery to allow active transport within the cell, such as kinesin walking along microtubules . A biological example of diffusion is the gas exchange that occurs during respiration within the human body. Upon inhalation, oxygen is brought into
1363-409: The concentration gradient of these substances, each moving away from their respective areas of higher concentration toward areas of lower concentration. Cellular respiration is the cause of the low concentration of oxygen and high concentration of carbon dioxide within the blood which creates the concentration gradient. Because the gasses are small and uncharged, they are able to pass directly through
1410-423: The concentration gradient" (compared with active transport , which often moves material from area of low concentration to area of higher concentration, and therefore referred to as moving the material "against the concentration gradient"). However, in many cases (e.g. passive drug transport) the driving force of passive transport can not be simplified to the concentration gradient. If there are different solutions at
1457-472: The cytosol across the porous outer mitochondrial membrane to the intermembrane space, but must utilize CACT to cross the nonporous inner mitochondrial membrane and reach the mitochondrial matrix. CACT is a cotransporter , returning one molecule of carnitine from the matrix to the intermembrane space as one molecule of fatty acyl–carnitine moves into the matrix. A disorder is associated with carnitine-acylcarnitine translocase deficiency . This disorder disrupts
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1504-472: The dissolution of the drug and may affect the degree of chemical degradation of the drug by intestinal microflora. Disease states affecting liver metabolism or gastrointestinal function will also have an effect. Other factors may include, but are not limited to: Each of these factors may vary from patient to patient (inter-individual variation), and indeed in the same patient over time (intra-individual variation). In clinical trials , inter-individual variation
1551-452: The drug be given intravenously. Intravenous administration of a developmental drug can provide valuable information on the fundamental pharmacokinetic parameters of volume of distribution ( V ) and clearance ( CL ). In pharmacology, relative bioavailability measures the bioavailability (estimated as the AUC ) of a formulation (A) of a certain drug when compared with another formulation (B) of
1598-400: The drug taker's absorption rate, the bottom value of the deviation range is used in order to ensure the intended efficacy, unless the drug is associated with a narrow therapeutic window . For dietary supplements , herbs and other nutrients in which the route of administration is nearly always oral, bioavailability generally designates simply the quantity or fraction of the ingested dose that
1645-446: The environment when they are adsorbed to soil minerals or partition into hydrophobic organic matter. Absolute bioavailability compares the bioavailability of the active drug in systemic circulation following non- intravenous administration (i.e., after oral , buccal, ocular, nasal, rectal, transdermal , subcutaneous , or sublingual administration), with the bioavailability of the same drug following intravenous administration. It
1692-503: The environment). A noteworthy example for agriculture is plant phosphorus deficiency induced by precipitation with iron and aluminum phosphates at low soil pH and precipitation with calcium phosphates at high soil pH. Toxic materials in soil, such as lead from paint may be rendered unavailable to animals ingesting contaminated soil by supplying phosphorus fertilizers in excess. Organic pollutants such as solvents or pesticides may be rendered unavailable to microorganisms and thus persist in
1739-496: The human body. There are many other types of glucose transport proteins , some that do require energy , and are therefore not examples of passive transport. Since glucose is a large molecule, it requires a specific channel to facilitate its entry across plasma membranes and into cells. When diffusing into a cell through GLUT2, the driving force that moves glucose into the cell is the concentration gradient. The main difference between simple diffusion and facilitated diffusion
1786-404: The intravenous dose to be administered with a minimum of toxicology and formulation. The technique was first applied using stable-isotopes such as C and mass-spectrometry to distinguish the isotopes by mass difference. More recently, C labelled drugs are administered intravenously and accelerator mass spectrometry (AMS) used to measure the isotopically labelled drug along with mass spectrometry for
1833-546: The pharmaceutical industry. The pharmacological definition cannot apply to these substances because utilization and absorption is a function of the nutritional status and physiological state of the subject, resulting in even greater differences from individual to individual (inter-individual variation). Therefore, bioavailability for dietary supplements can be defined as the proportion of the administered substance capable of being absorbed and available for use or storage. In both pharmacology and nutrition sciences, bioavailability
1880-418: The proteins, have any chance of being filtered through. On the other hand, the membrane pores of liver cells are extremely large, but not forgetting cells are extremely small to allow a variety of solutes to pass through and be metabolized. Osmosis is the net movement of water molecules across a selectively permeable membrane from an area of high water potential to an area of low water potential. A cell with
1927-407: The ratio of the mean responses (usually of AUC and the maximum concentration, C max ) of its product to that of the "brand name drug" is within the limits of 80% to 125%. Where AUC refers to the concentration of the drug in the blood over time t = 0 to t = ∞, C max refers to the maximum concentration of the drug in the blood. When T max is given, it refers to the time it takes for
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1974-429: The same drug, usually an established standard, or through administration via a different route. When the standard consists of intravenously administered drug, this is known as absolute bioavailability (see above ). Relative bioavailability is one of the measures used to assess bioequivalence ( BE ) between two drug products. For FDA approval, a generic manufacturer must demonstrate that the 90% confidence interval for
2021-402: The systemic drug concentrations achieved from the non-labelled oral dose). The intravenous and oral concentrations can then be deconvoluted by virtue of their different isotopic constitution, and can thus be used to determine the oral and intravenous pharmacokinetics from the same dose administration. This technique eliminates pharmacokinetic issues with non-equivalent clearance as well as enabling
2068-413: The true extent of systemic absorption (referred to as absolute bioavailability) is clearly useful, in practice it is not determined as frequently as one may think. The reason for this is that its assessment requires an intravenous reference ; that is, a route of administration that guarantees all of the administered drug reaches systemic circulation. Such studies come at considerable cost, not least of which
2115-442: The two sides of the membrane with different equilibrium solubility of the drug, the difference in the degree of saturation is the driving force of passive membrane transport. It is also true for supersaturated solutions which are more and more important owing to the spreading of the application of amorphous solid dispersions for drug bioavailability enhancement. Simple diffusion and osmosis are in some ways similar. Simple diffusion
2162-504: The unlabelled drug. There is no regulatory requirement to define the intravenous pharmacokinetics or absolute bioavailability however regulatory authorities do sometimes ask for absolute bioavailability information of the extravascular route in cases in which the bioavailability is apparently low or variable and there is a proven relationship between the pharmacodynamics and the pharmacokinetics at therapeutic doses. In all such cases, to conduct an absolute bioavailability study requires that
2209-421: The water moves into the cell, down its concentration gradient (from higher to lower water concentrations). That can cause the cell to swell. Cells that don't have a cell wall, such as animal cells, could burst in this solution. A hypertonic solution is when the solute concentration is higher (think of hyper - as high) than the concentration inside the cell. In hypertonic solution, the water will move out , causing
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