Bioavailability and Bioequivalence

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1. Bioavailability

1.2. Intravenous vs. other route

If the same API, as shown in Figure 1, is given via another route, such as a tablet given orally (by mouth), the bioavailability is lower than 100% and the time course is different (Figure 2).

A graphic showing the bioavailability as the concentration over time (in hours) for medicines given orally.

oral bioavailability

Figure 2: The concentration of medicine (in % of dose administered)  in the blood for a tablet taken orally, and observed over the period of 15 hours. The area under the curve (AUC) is shaded. Tmax is the time when the highest concentration of the medicine is found in the blood, Cmax the maximum concentration.

The lower bioavailability of the oral route compared to injection is explained in the following example from Figure 3. After a tablet or capsule is swallowed, it reaches the stomach within a minute or two. In the stomach, it is then dissolved and some of the active substance is absorbed into the bloodstream.

An image which compares the absorption of medicine from an intravenous injection with that of a medicine from a capsule taken orally.

oral vs intravenous bioavailability

Figure 3: Schematic illustration of absorption from a capsule taken orally (by mouth) versus injection directly into the bloodstream (IV). After reaching the stomach, the capsule is further transported to the small intestine, where further absorption occurs.

After some time in the stomach, the components are transported to the small intestine. Here they will be fully absorbed. Absorption from the gastrointestinal tract can vary greatly. A poor absorption or a lack of absorption from the stomach and the intestines can lower the bioavailability. When the API is absorbed, it first reaches the hepatic portal vein, and is then transported to the liver. This is the first time the active substance is metabolised in the liver, which is called the ‘first pass metabolism’. Some APIs are metabolised more than others during this first pass metabolism. The non-metabolised part of the active substance, normally less than 100%, will reach systematic circulation via the hepatic vein. The amount that actually reaches systemic circulation is referred to as the ‘absolute bioavailability’.