Abstract
One of the most important pharmacokinetic characteristics of a drug or new drug candidate is its oral bioavailability. The oral route is the preferred means of administration for most drug therapies, particularly those self-administered by the patient on an ongoing basis. Unless a drug is intended to treat a condition of the gastrointestinal tract, its effectiveness after oral administration requires attaining adequate and consistent systemic exposure. The extent of bioavailability determines the levels of exposure as well as the variability in exposure. Hellriegel et al. (1996) surveyed 143 literature references reporting absolute oral bioavailability and described the relationship between absolute bioavailability and inter-subject variability (% CV) for 100 drugs studied in those references. It was shown that the variability of systemic exposure after oral dosing was greatest when oral bioavailability was low and, conversely, inter-subject variability was generally low when oral bioavailability was high. Variability of systemic exposure leads to inconsistent and possibly unpredictable pharmacological and toxicological effects of the drug. Therefore, drugs with good oral bioavailability can have a considerable therapeutic advantage over related drugs with poor oral bioavailability.
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Aungst, B.J., Matz, N. (2007). Prodrugs to Reduce Presystemic Metabolism. In: Stella, V.J., Borchardt, R.T., Hageman, M.J., Oliyai, R., Maag, H., Tilley, J.W. (eds) Prodrugs. Biotechnology: Pharmaceutical Aspects, vol V. Springer, New York, NY. https://doi.org/10.1007/978-0-387-49785-3_8
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