Significance of Bioavailability in Clinical Practice and Drug Development

In clinical practice, knowledge of the bioavailability of a drug is obviously important for dose calculation. If we administer a dose of the drug (D) to a patient but do so via a route for which bioavailability = F, the actual amount delivered will be:

Delivered drug = D x F

In drug development, a high oral bioavailability is desirable. The main problem with low bio-availability is the potential for inter-individual variation. If a drug has an average oral bioavailability of (say) 98%, then individual patients will have values scattered around this figure, with most values in the high 90s and very few patients likely to show values less than 90%. With bio-availability values of 90-100%, we are faced with only 10% variability which is unlikely to cause any practical problems. However, if the mean availability is only 40%, individual values could easily be as low as 30% or as high as 60%. We now have a situation where the same oral dose of the drug will deliver twice as much drug to one patient as another. A discrepancy as large as this is likely to make dose optimization for individual patients a complex process and the product will be less attractive to medical practitioners.

The first thing to note is that bio-availability is reported as a proportion. So, if a quarter of the administered dose eventually gets into the circulation, its bioavailability could be quoted as 0.25 or 25%. Either value is perfectly acceptable, but notice that in any pharmacokinetic calculation where a value for bioavailability has to be incorporated, it must be in the decimal form (0.25, not 25).

Finally, the definition requires the drug to reach the ‘systemic blood circulation: What this means is the general or well-mixed circulation, not some obscure backwater. The requirement for this term will be more obvious, once we have considered oral bioavailability in more.

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