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20-September-2008 09:55:50 - Bioavailability In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via other routes such as orally, its bioavailability decreases due to incomplete absorption and first-pass metabolism. Bioavailability is one of the essential tools in pharmacokinetics, as bioavailability must be considered when calculating dosages for non-intravenous routes of administration. Contents 1 Definition 2 Absolute bioavailability 3 Relative bioavailability 4 Factors influencing bioavailability 5 See also 6 References Definition Bioavailability is a measurement of the extent of a therapeutically active drug that reaches the systemic circulation and is available at the site of action.1 It is expressed as the letter F. Absolute bioavailability Absolute bioavailability compares the bioavailability estimated as area under the curve, or AUC of the active drug in systemic circulation following non-intravenous administration i.e., after oral, rectal, transdermal, subcutaneous administration, with the bioavailability of the same drug following intravenous administration. It is the fraction of the drug absorbed through non-intravenous administration compared with the corresponding intravenous administration of the same drug. The comparison must be dose normalized if different doses are used; consequently, each AUC is corrected by dividing the corresponding dose administered. In order to determine absolute bioavailability of 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 non-intravenous administration. The absolute bioavailability is the dose-corrected area under curve AUC non-intravenous divided by AUC intravenous. For example, the formula for calculating F for a drug administered by the oral route po is given below. F = \fracAUC_podose_IVAUC_IVdose_po Therefore, a drug given by the intravenous route will have an absolute bioavailability of 1 F=1 while drugs given by other routes usually have an absolute bioavailability of less than one. Relative bioavailability This measures the bioavailability estimated as area under the curve, or AUC of a certain drug when compared with another formulation of 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. \mathitrelative\ bioavailability = \fracAUC_Adose_BAUC_Bdose_A Factors influencing bioavailability The absolute bioavailability of a drug, when administered by an extravascular route, is usually less than one i.e. F1. Various physiological factors reduce the availability of drugs prior to their entry into the systemic circulation, Such factors may include, but are not limited to: Physical properties of the drug hydrophobicity, pKa, solubility The drug formulation immediate release, excipients used, manufacturing methods, modified release - delayed release, extended release, sustained release, etc. If the drug is administered in a fed or fasted state Gastric emptying rate Circadean differences Enzyme induction/inhibition by other drugs/foods: Interactions with other drugs e.g. antacids, alcohol, nicotine Interactions with other foods e.g. grapefruit juice, pomello, cranberry juice Transporters: Substrate of an efflux transporter? e.g. P-glycoprotein Health of the GI tract Enzyme induction/inhibition by other drugs/foods: Enzyme induction increase rate of metabolism. e.g. Phenytoin antiepileptic induces CYP1A2, CYP2C9, CYP2C19 and CYP3A4 Enzyme inhibition decrease rate of metabolism. e.g. grapefruit juice inhibits CYP3A -- higher nifedipine concentrations Individual Variation in Metabolic Differences Age: In general, drugs metabolized more slowly in fetal, neonatal, and geriatric populations Phenotypic differences, enterohepatic circulation, diet, gender. Disease state e.g. hepatic insufficiency, poor renal function Each of these factors may vary from patient to patient inter-individual variation, and indeed in the same patient over time intra-individual variation. Whether a drug is taken with or without food will affect absorption, other drugs taken concurrently may alter absorption and first-pass metabolism, intestinal motility alters 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. Relative bioavailability is extremely sensitive to drug formulation. Relative bioavailability is one of the measures used to assess bioequivalence between two drug products, as it is the Test/Reference ratio of AUC. The maximum concentration of drug in plasma or serum Cmax is also usually used to assess bioequivalence. See also ADME-Tox Lipinski's Rule of 5 Biopharmaceutics Classification System Caco-2 http://www.nottingham.ac.uk/nursing/sonet/rlos/bioproc/metabolism/default.html References ^ Shargel, L.; Yu, A.B. 1999. Applied biopharmaceutics pharmacokinetics 4th ed.. New York: McGraw-Hill. ISBN 0-8385-0278-4 January 2008 v d e Topics in Medicinal Chemistry ADME · Bioavailability · Chemogenomics · Drug design · Drug discovery · Enzyme inhibitor · Mechanism of action · New chemical entity · Pharmacodynamics · Pharmacokinetics · Pharmacology · Pharmacophore · Quantitative structure-activity relationship Retrieved from http://en..org/wiki/Bioavailability Categories: Pharmacokinetics | Medicinal chemistryHidden category: Articles needing additional references from January 2008 Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages العربية Català Deutsch Español Français Galego Italiano Nederlands 日本語 ‪Norsk bokmÃ¥l‬ Polski Português SlovenÅ¡Ä?ina СрпÑ?ки / Srpski Suomi Svenska ไทย Türkçe ä¸æ–‡ This page was last modified on 9 August 2008, at 23:54
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