Bioavailability

Bioavailability after intravenous administration (by definition 100%, red, i.v.) and after oral administration (black, grey, p.o.): If the areas under the curves for the period ${0-\infty }$ are equal for both methods of administration, the oral bioavailability also corresponds to 100% (grey area under black curve). Smaller areas correspond to lower bioavailability. $c_{t}=$ drug concentration in plasma, $t=$ time.

Bioavailability is a key concept in pharmacology and nutrition, referring to the rate and extent to which a substance is absorbed into the bloodstream and made available at the site of physiological activity. This concept is crucial for both pharmaceuticals and nutraceuticals, as it determines the effectiveness of drugs and dietary supplements.

Definition and Significance

Bioavailability is a term used to describe the proportion of a nutrient or medication that, after being administered, enters the circulation and is thus able to exert its intended effect. This measure is essential for understanding the efficacy of any compound taken orally, intravenously, or through other routes of administration.

• For Pharmaceuticals: In medication, high bioavailability ensures that a drug can effectively target the intended site in the body.
• For Nutraceuticals: In dietary supplements, it determines how well a nutrient is absorbed and utilized by the body.

Factors Affecting Bioavailability

Several factors can influence the bioavailability of a substance:

• Chemical Form: The molecular structure of a compound can significantly affect its absorption. For example, certain vitamins are better absorbed in specific forms.
• Route of Administration: Oral, intravenous, sublingual, and topical are different ways drugs can be administered, each with varying bioavailability.
• Metabolism: First-pass metabolism in the liver can reduce the concentration of a substance before it reaches systemic circulation.
• Solubility: Water-soluble compounds tend to have higher bioavailability than fat-soluble ones.
• Interactions: Interactions with other substances, like food or other drugs, can enhance or hinder absorption.

Measuring Bioavailability

Bioavailability is often assessed through specific pharmacokinetic studies, which evaluate the concentration of a drug in plasma over time. The two key metrics used are absolute and relative bioavailability.

Absolute Bioavailability

This measures the bioavailability of a drug compared to its intravenous administration. The formula for calculating absolute bioavailability (F) is:

$F={\frac {AUC_{\text{oral}}\times Dose_{\text{IV}}}{AUC_{\text{IV}}\times Dose_{\text{oral}}}}\times 100\%$

where AUC is the area under the plasma concentration-time curve for oral (AUC_oral) and intravenous (AUC_IV) administration, and Dose refers to the dose administered via each route.

Relative Bioavailability

Relative bioavailability compares the bioavailability of a drug in different formulations, typically against a standard or reference formulation. The formula is:

$F_{\text{rel}}={\frac {AUC_{\text{test}}\times Dose_{\text{ref}}}{AUC_{\text{ref}}\times Dose_{\text{test}}}}\times 100\%$

where AUC_test and AUC_ref are the areas under the curve for the test and reference formulations, respectively, and Dose is the dose for each.

Factors Affecting Bioavailability

Bioavailability (F) of oral drugs or bioactive food components is influenced by several key stages: liberation, absorption, distribution, metabolism, and elimination. The equation representing bioavailability is:

$F=F_{C}\times F_{B}\times F_{A}\times F_{M}$

Where each factor represents a different aspect of how a substance is processed in the body:

• F_C (Liberation): This is the fraction of a micronutrient or drug that becomes available from its food matrix or dosage form in the GIT. It's influenced by factors like the physical and chemical form of the substance, processing methods, and the presence of other components that might bind or interact with the nutrient or drug.
• F_B (Bio-accessibility): This refers to the portion of the substance that is released from the food product or dosage form and then dissolves in the GIT liquids, making it available for absorption. This stage is affected by various factors including the pH and enzyme activity in the GIT, as well as the solubility and stability of the nutrient or drug in the intestinal environment.
• F_A (Absorption): This is the fraction of the substance that passes through the intestinal wall into the systemic circulation. Factors influencing absorption include the integrity of the gastrointestinal mucosa, the presence of transporters and enzymes, and the physicochemical properties of the substance like molecular size, lipophilicity, and charge.
• F_M (Metabolism): This represents the fraction of the substance that remains in a bioactive form after undergoing metabolic transformations. This includes changes due to enzymatic activity within the GIT, as well as liver metabolism and systemic circulation. The metabolic stability of a compound and its susceptibility to enzymatic degradation are key factors here.

Each of these stages is crucial in determining the overall bioavailability of a substance, and they are influenced by the chemical breakdown of bioactive elements during processing, manufacture, storage, and transport, as well as interactions within the GIT.

Improving Bioavailability

Research and development in pharmaceutical and nutraceutical sciences focus on enhancing bioavailability through various means, including advanced delivery systems, chemical modifications, and combinational approaches.

• Nano-Based Delivery Systems: Delivery systems utilizing of nanotechnology (e.g. liposomes, micelles) to enhance the delivery and bioavailability of various nutrients and bioactive components.
• Chemical Modifications: Altering the chemical structure of a compound can increase its solubility and absorption, making the active ingredient more available in the systemic circulation.
• Combinational Approaches: Using adjuvants or combining nutrients with enhancers can significantly improve bioavailability. This approach often involves synergistic combinations that enhance the overall effect of the active ingredients.

Conclusion

Understanding and optimizing bioavailability is fundamental for the effectiveness of drugs and nutritional supplements. As research progresses, new methods and formulations continue to emerge, enhancing the efficacy of therapeutic and nutritional interventions.

See Also

• Area Under the Curve (AUC)
• Nano‐Based Delivery Systems
• Wikipedia - Bioavailability