Clinical Trial Essentials: Utilizing Bioavailability Assays To Determine The Rate Of Drug Absorption
Drug products are often administered extravascularly and are intended to act systemically. Hence, drug absorption becomes crucial for elucidating the intended pharmacological effect. Drug loss or delay in absorption may affect drug responses and result in drug failure. Researchers use bioavailability assay to determine the rate of drug absorption during different steps of drug discovery.
But what does bioavailability mean?
Bioavailability is the rate and extent to which a drug molecule enters the systemic circulation and becomes available at the site of action. Bioavailability largely depends on the dosage form, which is determined successively by the manufacturing and design of the drug product. Differences in formulations affect the bioavailability of the compound. Hence, knowing drug formulation is vital for bioequivalence CRO to assess equivalence between two drug compounds.
There are three aspects to assessing equivalence; chemical, bioequivalence, and therapeutic equivalence. Chemical equivalence demonstrates that two drug products have the same active compound in similar amounts. Bioequivalence indicates that when two drug products are administered to the same patient at the same doses will result in the same drug concentrations in the tissues and plasma. Therapeutic equivalence demonstrates that the two drug products will generate the same therapeutic effects under similar conditions.
In vivo bioequivalence studies are crucial to demonstrate bioequivalence. In vivo bioequivalence testing is necessary for the approval of generic drug products. Although bioequivalent drug products are therapeutically equivalent, some nonequivalence can be observed during long-term studies with patients stabilized on one formulation and when a nonequivalent substitute is administered. Thus bioavailability/bioequivalence (BA/BE) studies in clinical research become essential for all drug products.
Assessing bioavailability for the rate of drug absorption
The gastrointestinal membrane is the barrier between the drug and the blood. Hence, the drug’s ability to pass through the membrane is crucial for its absorption. Drug dissolution becomes a vital necessity for a drug product to be absorbed in the blood. Any factor that affects the dissolution of a drug product is likely to influence the rate of drug absorption. These factors include physicochemical properties of the drug product, pH of the site of drug administration, nature of the GI membrane, and physiological characteristics.
Bioavailability is determined generally through the area under the plasma concentration-time curve (AUC). AUC is the most reliable measure to assess bioavailability during different steps of drug development. AUC is proportional to the amount of unchanged drugs reaching the systemic circulation. Researchers consider two drug products as bioequivalent when their AUC curves are superimposable.
The drug plasma concentration will increase as the drug reaches the blood. The blood drug concentration reaches its peak when the absorption rate and elimination rate are equal. Generally, peak plasma drug concentration is considered as the index of absorption rate in bioavailability studies.
With urinalysis, bioavailability can be assessed through drugs that are excreted unchanged in the urine. Researchers measure the amount of excreted drugs after an initial dose. Ideally, 7-10 elimination half-lives are considered for collecting urine. Researchers can estimate bioavailability after multiple dosages and measure the unchanged drug in the urine.