Bioavailability - an overview | ScienceDirect Topics (2024)

Abstract

Bioavailability, i.e., the fraction of absorbed and utilized micronutrients, is particularly important for nonheme iron and provitamin A carotenoids as bioavailability varies widely depending on a number of factors. Stable (nonradioactive) isotope techniques to assess bioavailability of these micronutrients have contributed significantly to a better understanding of the importance of integrating bioavailability into the development of food-based strategies to combat iron and vitamin A deficiencies. In this article, the authors discuss the basic principles of stable isotope techniques to assess bioavailability of nonheme iron and provitamin A carotenoids and highlight important findings based on these techniques to move the agenda forward.

Importance of Nutrient Bioavailability to Human Nutrition

Assessment of bioavailability of nutrients is an essential component of deriving dietary reference intakes (DRIs), guidelines for optimal intake of individual nutrients established for North American populations. Many DRIs are based on evaluation of available physiological data to determine the obligatory daily needs for a nutrient to replace losses, or the amount needed for optimal growth of tissues, and an estimate of overall dietary bioavailability of the nutrient in question. In many populations, the content of a nutrient in the diet (e.g., iron or zinc) may be sufficient to meet recommended intake, but bioavailability is suboptimal due to the presence of high levels of inhibitory substances (such as phytate) in the diet leading to a high risk of developing this nutrient deficiency.

Abstract

Bioavailability, uptake, metabolism, storage, and excretion of chemicals constitute toxico*kinetics. Bioavailability is the potential for uptake of a substance by a living organism. It is usually expressed as the fraction that can be taken up by the organism in relation to the total amount of the substance available. In pharmacology, the bioavailability is the ratio of the amount of a compound in circulation after its extravenous application and its intravenous injection. In aquatic toxicology, environmental bioavailability is usually relevant. Factors affecting the bioavailability of a chemical depend on the route of uptake, and whether the chemical is in the bottom sediment, dissolved in water, or is a constituent of the organisms. In the case of water-soluble substances, the primary source of toxicant is water, and the bioavailability depends on complex formation, especially with humic substances. Even when water-soluble substances are sediment bound, they reside mainly in pore water. Lipid-soluble substances are taken up especially from sediment or from other organisms. The bioavailability from water decreases with increasing lipophilicity and with increasing amount of dissolved organic carbon or colloids in the aquatic phase. With regard to sediment, both the sediment properties (e.g. grain size) and the amount of organic material in the sediment affect bioavailability. The main abiotic factors affecting bioavailability are oxygenation and pH. As an example, metal speciation, affecting bioavailability, depends very much on the pH.

Bioavailability (F)

Bioavailability is a term used to describe the percentage (or the fraction (F)) of an administered dose of a xenobiotic that reaches the systemic circulation. Bioavailability is practically 100% (F=1) following an intravenous administration. Bioavailability could be lower (F≤1) and in some cases almost negligible for other routes (e.g., oral and dermal), depending on how efficiently a xenobiotic crosses various biological membranes (e.g., skin and stomach). Additionally, whether or not tissues or organs (e.g., skin and liver), through which xenobiotics pass before reaching the systemic circulation, are capable of metabolizing the substance. Thelatter phenomenon is known as a first-pass effect. Bioavailability may vary considerably between xenobiotics or even between batches of a given xenobiotic. For example, therapeutic drugs must undergo bioavailability testing to ensure reliable dosing throughout treatment. The blood concentration of the administered drug is used as an index of bioavailability.

Bioavailability (The Drug has to be ‘Available’ at The Site of Intended Action)

Bioavailability is expressed as the percentage of the total drug dose administered that reaches the circulation. For a drug taken orally, the ‘first-pass effect’ of hepatic metabolism reduces bioavailability. The bioavailability calculations include both free and bound forms of the drug. A systemic drug with a relatively low bioavailability is acyclovir; the prodrug for acyclovir, valacyclovir, has at least three times greater bioavailability. At the other end of the spectrum are the fluoroquinolones, for which oral absorption (and resultant bioavailability) is so complete that the oral and intravenous doses for many members of this drug group are identical. A more optimal method (if it were more practical) would be to calculate bioavailability at the site of intended action; for drugs discussed in this book, it would be based on tissue levels at the site of intended action, the various skin structures. At present such ‘ideal’ bioavailability calculations are not routinely available.

For most chapters in this book that discuss systemic drugs there are tables that present data for the following: (1) % bioavailable and (2) % protein binding. The ‘% bioavailable’ is typically factored into ideal oral drug dosage calculations, which will produce circulating drug levels in a reasonably safe and effective ‘therapeutic range.’ The ‘% protein binding’ is important to the subject of drug interactions as previously discussed, with methotrexate as an important example. Changes in albumin levels in disease states such as severe liver or renal disease will often necessitate drug dosage adjustments for drugs (such as methotrexate) that are highly protein bound.

Creating drug formulations with a more optimal bioavailability is a daunting task for the pharmaceutical industry. In the past few decades there have been updated formulations of older drugs with higher bioavailability, more predictable bioavailability, or both. For drugs with a relatively narrow therapeutic index (cyclosporine, methoxsalen), improved predictability of the drug absorption and resultant bioavailability are very important. The release of Neoral and Gengraf (in place of the previous cyclosporine formulation, Sandimmune) is an example for both improved % bioavailability and more predictable bioavailability of the newer formulation. Likewise, Oxsoralen Ultra demonstrates improvement in both of these two parameters. In a separate example, the need for improved efficacy from griseofulvin led to the progression from the original griseofulvin formulations → microsize formulations → ultramicrosize formulations. Each step of this progression resulted in improved bioavailability and smaller griseofulvin dosages required for an adequate therapeutic response.

Bioavailability (F)

Bioavailability is a term used to describe the percentage (or the fraction F) of an administered dose of a xenobiotic that reaches the systemic circulation. Bioavailability is practically 100% (F=1) following an intravenous administration. Bioavailability could be lower (F⩽1) and in some cases almost negligible for other routes (e.g., oral, dermal, and pulmonary), depending on how efficiently a xenobiotic crosses various biological membranes (e.g., lungs, skin, and stomach) or whether or not tissues or organs (e.g., lungs, skin, and liver) through which xenobiotics pass before reaching the systemic circulation are capable of metabolizing the substance; the latter phenomenon is known as a first-pass effect. Bioavailability may vary considerably between compounds or even between batches of a given compound. For example, drugs commonly used as therapeutic agents must undergo bioavailability testing to ensure reliable dosing throughout treatment. The blood concentration of the administered drug is used as an index of bioavailability.

E Bioavailability

Bioavailability is (1) the fraction of an administered dose of a drug that reaches the systemic circulation as intact drug (expressed as F) and (2) the rate at which this occurs. As an i.v. dose is injected directly into the systemic circulation, the bioavailability of an i.v. dose is by definition 100 percent (F=1). For all other routes of administration, bioavailability is determined by the extent of drug absorption (being the result of both drug uptake from the administration site and possible first-pass effects; see Section III.D.), and varies between 0 and 100 percent (0 < F < 1). For example, orally administered morphine has a bioavailability of about 25 percent due to significant first-pass metabolism in the liver. Therefore, the dose of morphine given orally is usually 3–5 times larger than an i.v. dose of morphine.

For example, if the AUC_oral is 25 percent of the AUC_i.v., the bioavailability of the oral formulation is 25 percent (F=0.25).

Obviously, the relative bioavailability of a formulation is not equal to F (the fraction of the dose that reaches the systemic circulation), as the absolute bioavailability of the reference formulation might be quite low due to poor absorption and/or first-pass metabolism.

Abstract

Bioavailability (BA) and bioequivalence (BE) studies are essential in oral dosage form development. This chapter provides readers an overview of general concept of BA and BE. Details on typical BA/BE study designs, study conducts, bioassays, and data analyses are discussed, with a primary focus on orally administered drugs. Special topics on BE for narrow therapeutic drugs and highly variable drugs, together with application of partial areas under the curve for BE testing are also presented. In addition, issues related to biowaiver are discussed in details.

8.5.1 Bioavailability

Bioavailability is the major factor affecting dietary requirements (Sandstrom, 1997). Flesh foods facilitate bioavailability, although indigestible Zn-binding ligands decrease bioavailability (Mills, 1985). Examples of indigestible Zn-binding ligands are phytate, certain dietary fibers (Sandstrom, 1997), lignin (Reinhold et al., 1976), and Maillard browning products (Lykken et al., 1986; Reinhold and Garcia, 1979). Foods rich in Ca and phytate, such as corn tortillas, are potent inhibitors of Zn absorption (Solomons et al., 1979). Dietary phytate/Zn, and phytate × Ca/Zn molar ratios are predictive of bioavailability of dietary Zn (Gibson et al., 1991; Ferguson et al., 1989). By current use, a phytate/Zn molar ratio <5 is consistent with high Zn bioavailability, although a ratio >15 is consistent with poor Zn bioavailability (Committee, 1996). Other factors that affect Zn bioavailability include high concentrations of ferrous iron in Fe supplements (Solomons, 1986; Solomons, 1986), high intakes of Ca (Wood and Zheng; 1997; Spencer et al., 1984), and pharmacological intakes of folic acid (Milne et al., 1984; Simmer et al., 1987).

Abstract

Bioavailability aims to describe the effect of metabolic events on nutrient utilization. The supply of nutrients to the human body depends not only on the amount of a nutrient in food but also on its bioavailability. The bioavailability of nutrients is highly variable and can be influenced by numerous factors. Different nutrients (including protein, iron, and vitamin A), and the forms in which they exist in the ingested medium, will react in different ways to inhibitors and enhancers as well as the host's nutritional status, all of which contribute to nutrient bioavailability.