Although knowing 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 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 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 the intravenous dose to be administered with a minimum of toxicology and formulation.

The technique was first applied using stable-isotopes such as 13 C and mass-spectrometry to distinguish the isotopes by mass difference. More recently, 14 C labelled drugs are administered intravenously and accelerator mass spectrometry AMS used to measure the isotopically labelled drug along with mass spectrometry for 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 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 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.

When T max is given, it refers to the time it takes for 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.

The absolute bioavailability of a drug, when administered by an extravascular route, is usually less than one i. 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 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. 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 is a critical measurement used to assess the bioavailability differences from patient to patient in order to ensure predictable dosing. Contents move to sidebar hide.

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Pharmacological measurement. Clinical Pharmacology During Pregnancy. doi : ISBN The Textbook of Pharmaceutical Medicine 6th ed. Jersey: BMJ Books. xPharm: The Comprehensive Pharmacology Reference. Equine Internal Medicine. Comprehensive Toxicology. The Journal of Nutrition.

PMID Carl-Gustaf Elinder was the author of this chapter in the 2nd edition of the Handbook on Toxicology of Metals; his text provided guidance. Handbook on the Toxicology of Metals. Bioavailability is the major factor affecting dietary requirements Sandstrom, Flesh foods facilitate bioavailability, although indigestible Zn-binding ligands decrease bioavailability Mills, Encyclopedia of Food Sciences and Nutrition.

Bioavailability strictly refers to both the uptake and metabolic utilization of a nutrient. New York: McGraw-Hill. Srini Plant and Soil. S2CID Bibcode : EnST In Betts, W. Biodegradation of Natural and Synthetic Materials. com or UL Solutions. The appearance of this content in the UL Prospector Knowledge Center does not constitute an endorsement by UL Solutions or its affiliates.

All content is subject to copyright and may not be reproduced without prior authorization from UL Solutions or the content author. The content has been made available for informational and educational purposes only. While the editors of this site may verify the accuracy of its content from time to time, we assume no responsibility for errors made by the author, editorial staff or any other contributor.

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UL Solutions does not warrant the performance, effectiveness or applicability of sites listed or linked to in any content. George Deckner brings over 40 years of experience as a formulating chemist to his role as a personal care and cosmetics industry expert at Prospector.

In addition to lending his industry expertise to Prospector, George consults with personal care and cosmetics suppliers. While at Procter and Gamble, he worked in skin care product development, global fragrance development, and most recently oral care product development in the Oral Care Advanced Technology Innovation Group.

Before being appointed a Victor Miles Research Fellow, he also served as Associate Director of Exploratory Formulation for skin care product development. He helped develop many of the core platform technologies used in skin care today with numerous products commercialized under the Olay, Bain de Soleil, Clearasil, Noxzema and SK2 brands.

Previously, George was a Senior Chemist and Manager in the area of skin care product development, as well as the Director of Exploratory Formulation for Charles of the Ritz Group. He is a frequent guest lecturer for numerous key global suppliers, as well as for local and national SCC meetings.

Learn more about Deckner Consulting Services…. Love your article! The content is very valuable. It shows that you spent time researching this and you have managed to turn it into an incredible piece of valuable content.

Will share with my audience. Share this article:      Improving active bioavailability is key to improving the efficacy of skin care formulations. Three factors that control the penetration rate of actives The three most important factors that control the skin penetration of actives are molecular weight, C log P and charge anionic or cationic.

Looking for actives for use in cosmetic formulations? Search for actives on Prospector. What formulations affect bioavailability?

Skin barrier disruption-the Stratum Corneum is comprised of layers of keratinocytes coated with epidermal lipids. Removing, penetrating, or changing the crystallinity or structure of this lipid layer will increase active penetration. Solvents: Dimethyl isosorbide, ethoxydiglycol, ethanol, oleic acid Phospholipids have consistently been shown to increase the skin penetration of both oil and water-soluble actives.

Examples include lecithin, hydrogenated lecithin, lysolecithin, and tocopheryl phosphate. Surfactant vesicles: Ssurfactants can form multilamellar and unilamellar vesicles with actives. Liposomes produced using phospholipids, cationic and nonionic surfactants are examples.

Hydration can reversibly swell corneocytes and change the structure of skin lipids and increase penetration 2. Examples include the use of humectants in formulations and the multilamellar liquid crystal based oil in water emulsions.

Occlusion: Dermatologists frequently recommend using Saran wrap to increase the efficacy of steroid creams on skin.

Physical or chemical exfoliation: Exfoliating skin before applying an active or using with an active can frequently increase product efficacy 3. Examples of chemical exfoliants include lactic, glycolic, salicylic acids, and N acetyl glucosamine.

Physical products include abrasive creams, sponges and electric or mechanical brushes. Increased solubility Molecular complexation: Cyclodextrins alpha, gamma, hydroxypropyl beta cyclodextrin have a molecular cavity that can encapsulate actives improving their water solubility.

The complexation is very specific to the chemical composition and shape of the active. Phytoglycogen has a cavity which can encapsulate many different types of actives.

Highly polar emollients are frequently needed to solubilize water insoluble actives since few are non-polar. Examples include isopropyl lauroyl sarcosinate, lauryl lactate, phenyl ethyl benzoate, dioctyl maleate, and dioctyl isosorbide.

Many sunscreens have also been shown to be penetration enhancers Increase the partitioning of active out of the formulation into skin: If an active is too compatible in the formulation, there is no driving force for it to leave the product film and penetrate.