What is Bioavailability?

Introduction to Bioavailability

Bioavailability is one of the many concepts pharmacy technicians are expected to know. It is one of the topics stated on the PTCB syllabus for the 2020 exam. Students must, therefore, have a solid understanding of this fundamental concept.

Definition: Bioavailability is the percentage of drug that reaches the systemic circulation (or cardiovascular system) to allow the drug to travel through blood vessels and other barriers to reach its target site of action. That target site depends on the drug and its mechanism of action.

For example:

• Amoxicillin has a bioavailability of 95 percent – meaning 95 percent of the drug reaches the systemic circulation. 5 percent of the active ingredient does not make it.
• The anti-depressant medicine, Prozac (fluoxetine), has a lower bioavailability, of approximately 70 percent – meaning 30 percent was metabolized/removed by the body before it reached its target site.
• Alendronic acid, a drug used to treat osteoporosis, has an exceptionally low bioavailability – of just 0.7 percent. This means that 94.3 percent of drug is, once it enters and travels through the body, lost in the process – with just 0.7 percent reaching the target site.

How a drug is administered to the body impacts how much drug is available at the target site. There are many different routes of administration: oral, inhalation, IV, IM, subcutaneous, buccal, rectal, and many more.

To give you an idea of the impact, let’s first compare what happens a drug when it is administered orally compared to when a drug is administered via the intravenous route.

Oral versus Intravenous Bioavailability

Drugs administered via the intravenous route have an almost or near 100 percent bioavailability. That is because there are almost no barriers to entry.

Compare that to the process of what orally administered drugs must go through. Drugs administered orally are under assault from:

• Mouth – enzymes within the oral cavity begin the breakdown process of the drug; the start of a breakdown marathon.
• Stomach – when the drug passes through the esophagus into the stomach, it is confronted by gastric acid which breaks down the drug even more.
• Intestine – as the drug passes through the stomach into the small intestine, it is confronted with even more enzymes from the pancreas, gall bladder, and intestine itself. Some drug will turn to waste and be removed via defecation. Drug that remains is absorbed through the upper part of the small intestine where it is shuttled to the liver.
• Liver – hepatic metabolism really goes to work on the drug. This is known as the first-pass effect. Drug must first-pass through the liver before it finally reaches the systemic bloodstream. There is a wide range of important enzymes in the liver – known as CYP 450 enzymes – that interact with and metabolize drugs. Once the metabolism process is complete, active ingredient passes into the bloodstream where it can now travel through and reach its target site.

Sometimes CYP 450 enzymes are intentionally exploited by drug manufacturers. For example – prodrugs are inactive drugs that, once administered to the body, are metabolized into their active form via many of these hepatic enzymes. The liver is doing the work for the drug manufacturer – turning the inactive prodrug into the active drug via these important CYP enzymes.

Once the liver has done its job, it hands a visa to the drug to enter the bloodstream. Drug can then meander its way through the bloodstream to reach its target site of action – where it can finally exert its therapeutic effect.

So, we can see there is a big difference between what happens a drug when it is administered via the oral route compared to when it is administered via the intravenous route.

Intravenous drug is injected direct into the bloodstream and so does not need to jump through loops of ongoing metabolism. Orally administered drugs must put themselves through an obstacle course:

• 100% of drug is available at the start of the course.
• Upon reaching the first hurdle (oral cavity), 20% of drug falls – leaving 80% left to complete the course.
• After the second (gastric acid) and third hurdles (small intestine/liver), another 50% of drug has fallen – leaving just 30% of drug to make it to the finish line (bloodstream/systemic circulation).

These effects are predictable and expected.

Factors that Impact Bioavailability

Drug manufacturers understand that not all drug will make it to the therapeutic site of action. They analyse drugs in immense detail. There are many different factors that influence how a drug will react to the body.

Factors that influence how a drug reacts with the body include:

• Physical properties of the drug – such as solubility and hydrophobicity (its propensity to repel against water; think of oil and water, for example – oil has a high degree of “hydrophobicity”).
• Diseases – particularly ones that affect the liver or gastrointestinal tract. For example – patients with liver disease are unable to metabolize drugs to the same extent as patients without liver disease. If you give the same dose to two patients, the patient with liver disease will be unable to metabolize the drug to the same extent and this increases the risk of toxicity and adverse effects.
• Age – older people metabolize drugs slower than younger people.
• Gender – women and men do not always metabolize drugs to the same extent, given physiological and hormonal differences between the two groups.
• Food – some drugs interact with food or should be taken on an empty stomach. Foods can contain enzymes that interact with the drug. The best example is grapefruit juice and statins. Grapefruit juice increases the risk of severe adverse effects with most statins due to the presence of compounds called furanocoumarins.
• Drug formulation – excipients are non-active ingredients and influence drug formulation. For example – binders, flavoring agents, coloring agents, preservatives – are all examples of excipients which, when combined with the active ingredient, form a medicine.

This is not an exhaustive list, but it provides a sound overview of the major factors that influence drug absorption and metabolism in the body.

Conclusion

Bioavailability is an important concept to know for the PTCB test.

There are 5 key take-home points to understand:

• The concept of bioavailability; the fraction of drug that reaches the systemic circulation after undergoing metabolism.
• Understanding the barriers to entry based on route of administration. For example – we learned that orally administered drugs have many barriers, whereas intravenous drugs have almost no barriers at all. Of course, there are many more routes of administration to consider, each of which has its own sets of barriers. Drugs taken via the rectal route, for example, avoid the gastrointestinal route which may otherwise have metabolized it.
• Knowing the first-pass effect; an effect where the liver metabolizes drug administered into the gastrointestinal tract before the drug is released into the bloodstream. CYP 450 enzymes play an important role in hepatic drug metabolism.
• Prodrugs – and what differentiates a prodrug from a drug. A prodrug is an inactive drug that needs to be converted to its active form by enzymes in the body, such as hepatic CYP 450 enzymes.
• Having a basic understanding of the factors that influence drug absorption, metabolism, and elimination (see above).

If you would like to practice PTCB test questions on bioavailability and every other topic in pharmacology, we have included a wide variety of relevant questions and full-length explained answers in our online course.

Check back to our PTCB Test Prep blog soon for more content to help you master the 2020 PTCB exam.