Clinical Pharmacology · MU Sofia

8. Clinical Drug Trials: evaluation of the bioavailability and bioequivalence of drugs.

Explains bioavailability as the rate and extent of absorption into the systemic circulation, with AUC, Cmax and Tmax, and the absolute and relative types. It then lists factors affecting absorption, from formulation and patient factors to interactions. The second part covers bioequivalence, the typical cross-over study design, the EMA 80–125% acceptance limits, and why generics and narrow therapeutic index drugs matter.

Inside: 2 sections · 2 tables · 15 flashcards · 2 min

Topic 8 of 30 in the MU Sofia syllabus for Clinical Pharmacology (Medicine, Year 5). The free AceMed note covers it in 2 sections, about 290 words (2 min of reading), with 15 flashcards.

In this note

  1. Bioavailability
  2. Bioequivalence

Bioavailability

Bioavailability (F) is the rate and extent to which the active substance is absorbed from a product and becomes available in the systemic circulation (and so at the site of action). By definition F = 100% for an IV dose.

What affects bioavailability

  • Drug and formulation: solubility, ionisation, particle size, dosage form (solutions fastest, then suspensions, capsules, tablets, enteric-coated forms slowest), immediate versus modified release.
  • Patient: gastric pH and emptying, GI motility and disease, food, age, first-pass metabolism in the gut wall and liver (e.g. nitroglycerin, morphine, propranolol have low oral F).
  • Interactions: food, antacids, chelation (tetracyclines with calcium), P-glycoprotein and CYP3A4 inhibitors and inducers.

Bioequivalence

Two products are bioequivalent when they contain the same active substance in the same amount and their bioavailabilities are so similar that their effects, both efficacy and safety, will be essentially the same. A generic medicine is approved by showing bioequivalence with the original (reference) product, instead of repeating large clinical trials.

The bioequivalence study

  • Usually a randomised, two-period, two-sequence, single-dose cross-over study in healthy volunteers (typically 24–36), with a wash-out of at least 5 half-lives between periods.
  • Frequent blood samples; AUC and Cmax for each product.
  • Acceptance (EMA): the 90% confidence intervals of the test/reference ratios of AUC and Cmax must lie within 80.00–125.00% (narrower, 90.00–111.11%, for narrow therapeutic index drugs). Differences in Tmax matter only if clinically relevant.

Why it matters

  • Bioequivalent products are therapeutically equivalent and interchangeable, so generics allow large cost savings.
  • Bioequivalence is a cheap, short substitute for clinical equivalence trials in large patient groups.
  • Caution when switching narrow therapeutic index drugs (antiepileptics, ciclosporin, levothyroxine, warfarin): monitor after a switch.

Bioequivalent means the same exposure (AUC and Cmax within 80–125%), and therefore the same effect: the basis for prescribing generics.

Read the full note free

The whole note, all 2 sections, is free with an AceMed account, with its 15 flashcards. Premium adds flashcard recall, highlights and Ask AI.

Start freeAlready a member? Open the note