Question

The H2 antagonist burimamide showed poor bioavailability in clinical trials.

(i) Define the term bioavailability. In your answer, distinguish bioavailablility
from bioactivity.
(ii) Protonation of the imidazole ring was identified as a reason for the low
bioavailability of burimamide. Explain, using appropriate structures, why
thiaburimamide, which features a sulfur atom in the alkyl chain, led to
increased bioavailability.

(iii) Thiaburimamide, also led to a modest increase in bioactivity. Propose a
reason for this increase in activity.

Answer 1

I)

Bioavailability is fraction of administered drug that reaches the systemic circulation or body's circulatory system.

It means it is rate at which drug is absorbed (chemically unchanged form).

For drug to be effective, it's active part must be absorbed and become available at site of action in required amount.

Hence, bioavailability plays important role in parmaceuticals. it is in vivo methodologies.

Bioactivity is - in vivo, in vitro, ex-vivo methodologies.

These are the events that take place during interaction with bio-molecules.

II)

Burimamide is antagonist at the H2 and H3 histamine receptors.

It means that they block the action of histamine at parietal stomach cells.

Its bioavailability is related to the pH and it is largely inactive at physiological pH.

H3 affinity is higher.

Thiaburimamide has Sulphur atom which prevent imidazole from protonation and increasing it's bioavailalbilty.