Bioavailability

Bioavailability (often abbreviated F) is a foundational pharmacokinetic parameter that describes the fraction of an administered medicine dose that reaches the systemic circulation unchanged. By definition, an intravenous dose has 100% bioavailability (F = 1.0), because it bypasses all absorption barriers and metabolism on the way to the bloodstream. All other routes of administration must be measured against this benchmark.

Oral bioavailability is the most commonly discussed and clinically relevant form. Several factors reduce it. First, the medicine must dissolve, cross the intestinal epithelium, and traverse the portal venous system to the liver. There, enzymes - particularly the cytochrome P450 system and conjugation enzymes - may metabolize a substantial fraction before the medicine reaches systemic circulation. This 'first-pass metabolism' can be modest (atorvastatin, F about 14%) or extreme (morphine, F about 25%; nitroglycerin, F less than 1%). Medicines with very low oral bioavailability are typically given by alternative routes (sublingual, transdermal, IV) when the high first-pass losses outweigh oral convenience.

Other routes have their own bioavailability profiles. Subcutaneous and intramuscular injections approach 100% for most medicines. Sublingual and buccal routes bypass first-pass metabolism, which is why nitroglycerin and buprenorphine can be effective sublingually at doses that would fail orally. Transdermal patches achieve sustained low-level absorption directly into systemic circulation. Inhaled medicines deliver high local concentrations to the lungs with variable systemic absorption.

Clinically, bioavailability matters when switching routes (IV to oral) or formulations (immediate to extended release). The conversion is rarely 1:1 - converting oral metoprolol to IV requires dividing the dose by approximately 2.5 to account for the difference in F. Bioavailability also drives concerns about food interactions: a high-fat meal can double the bioavailability of saquinavir but cut levothyroxine bioavailability by 30-40%. Medicine-medicine interactions involving CYP3A4 inhibitors (grapefruit juice, ketoconazole) can dramatically raise the bioavailability of substrates by reducing first-pass metabolism.

A common misconception is that generic medicines and brand-name medicines always have identical bioavailability. The FDA standard for bioequivalence allows the 90% confidence interval of the generic's bioavailability to fall between 80% and 125% of the reference product - a window that is acceptable for most medicines but can matter for narrow-therapeutic-index agents like warfarin, levothyroxine, and certain antiepileptic medicines. Another misconception is that high bioavailability is always desirable. Lower oral bioavailability is sometimes intentional - for example, in topical or inhaled steroids where systemic exposure is unwanted.

Prescribers consider bioavailability when choosing routes, adjusting doses, and counseling patients about food and medicine interactions.