Orally administered drugs, bioavailability

Area under the Curve (AUC) refers to the area under the curve in a plasma concentration-time curve. It is directly proportional to the amount of drug which has appeared in the blood ( central compartment ), irrespective of the route of administration and the rate at which the drug enters. The bioavailability of an orally administered drug can be determined by comparing the AUCs following oral and intravenous administration. 

First-pass metabolism is the elimination of an orally administed drug by the liver or sometimes the gut wall, before it reaches the systemic circulation. First-pass metabolism results in a decreased systemic bioavailability. 

First-pass effect (metabolism) The metabolism of a drug when it first passes through the liver. This is one of the major determinants of bioavailability for orally administered drugs. 

Medical scientists mainly rely on the measurement of bioavailability of a drug as a positive indicator of therapeutic equivalence, because clinical efficacy for orally administered drugs depends on the degree of absorption and the presence of the active ingredient in the blood stream. 

Guidance for Industry Bioavailability and Bioequivalence Studies for Orally Administered Drug Products—General Considerations. Oct. 2000. 

FDA. Guidance for Industry Bioavailability and Bioequivalence Studies for Orally Administered Drug Products—General Considerations (Revised) (I). Rockville MD, USA U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), 2003. 

FDA Guidance to Industry Bioavailability and bioequivalence studies for orally administered drug products — General considerations, 2002. 

Bioavailability is defined as the fraction of a given drug dose that reaches the circulation in unchanged form and becomes available for systemic dis-tributioa The larger the presystemic elimination, the smaller is the bioavailability of an orally administered drug. 

FIGURE 4.2 A Effect of differences in elimination rate ion the maximum concentration (C, J and time to maximum concentration (F ax) reached after a single oral dose. The drug absorption rate is the same (Ka = 1 h ) for curves A and B. The for curve A is 6 hours the P for curve B is 2 hours. B Differences between absorption rates can have a pronounced effect on the time (T ax) which the maximum concentration (C ,x) reached. Curve A shows an orally administered drug with an absorption rate 4 times faster than that of curve B. Curve C shows the effect of a 50% decrease in bioavailability of drug A. The half-life (4 hours) is similar for scenarios A-C. 

Efflux systems and presystemic metabolism are, beside other reasons, responsible for low bioavailability of orally administered drugs. Presystemic metabolism itself can be divided into three subtypes luminal metabolism, first-pass intestinal metabolism, and first-pass hepatic... 

The majority of orally administered drugs gain access to the systemic circulation by direct absorption into the portal blood. However, highly lipophilic compounds may reach the systemic blood circulation via the intestinal lymphatic system. The overall bioavailability of... 

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