Bioavailability Studies: Its Importance and Role

Drug development demands an in-depth understanding of the drug’s effect on the body and body’s impact on the drug. That’s where pharmacodynamic and pharmacokinetic studies step in. They help quantify the drug-body interaction and pave the way for informed “go/no-go” decisions.   

In pharmacokinetics, the drug’s time course and interaction with the body are determined. The quantification is targeted on four key processes, namely Absorption, Distribution, Metabolism, and Excretion, and hence, the moniker ADME. The ADME findings are crucial to determine the safety and efficacy of the candidate drug and calculating its appropriate dosage for patients.

Bioequivalence and bioavailability studies are the cornerstones of pharmacokinetics.

Bioavailability defined:

Once a drug is ingested, the First Pass Effect (FPE) comes into play, which is directly related to the gastrointestinal (GI) tract and liver. The FPE, in conjunction with partial absorption, brings down the drug concentration when it is rushed down the systemic circulation. Hence, only a fraction of the drug reaches the action site. The quantity of the drug’s active ingredient or moiety entering the systemic circulation about the dose administered is called bioavailability of drugs. It’s 100% for injectables but reduces significantly in orally administered drugs.

Bioavailability of drugs involves quantification of the candidate drug’s concentration in plasma, blood, and other matrices. A systemic protocol is adhered to, and findings are documented at specific time gaps. The data gleaned during bioavailability is leveraged for bioequivalence studies.

Bioequivalence defined:

For symptom relief from a given condition, physicians often substitute a standard drug with its generic version. The assurance that the substitute drug is as effective and safe as the standard drug stems from bioequivalence investigations. It’s a relative term, reflecting the difference in active ingredient or moiety at the action site when two similar medications are administered in the same molar doses under similar conditions. Simply put, bioequivalence probes how a candidate drug fares against the reference drug on safety, efficacy and quality parameters. If the two are bioequivalent, they can be interchanged for similar patient outcomes.

Role and importance:

Bioequivalence and bioavailability studies are the new interest zones in the drug development space. With applications across the entire drug development spectrum, from nonclinical trials to approval and beyond, it’s easy to guess why. Let’s elaborate on the role and importance.   

• Generic drug development:

Patent protection is applicable for a certain period only. Once over, generic variants of the patented drug can be developed, manufactured and marketed. Medications raking in .7 billion in annual sales went off patent in 2018, and the trend continues to gain traction.

The FDA mandates bioavailability of drugs and bioequivalence investigations for generic drug development through the Drug Price Competition and Patent Term Restoration Act, 1984.

The act empowers the FDA to approve a generic drug if the bioavailability and bioequivalence investigations indicate its therapeutic and safety equivalence with the patent drug.

• Quality assurance:

These investigations are integral to identify and determine the impact of manufacturing, storage and stability factors on how the drug interacts with the body, and vice-versa. The inferences are critical in the initial stages of marketing. The quantification of the candidate drug’s concentration in systemic circulation over a specified period in early clinical trials can help set standards for ensuing bioequivalence studies across the drug development pipeline.

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Maria Brown Joined: April 1st, 2020