Orally administered drugs

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. 

Altretamine has shown activity in the treatment of ovarian and lung cancer. This orally administered drug has the dose-limiting side effects of anorexia, nausea, vomiting, diarrhea, and abdominal cramping. Other side effects include neuropathy, agitation, confusion, and depression. 

Equation (35) describes the line in Fig. 10, which is a semilog plot of Cp versus time for an orally administered drug absorbed by a first-order process. The plot begins as a rising curve and becomes a straight line with a negative slope after 6 hours. This behavior is the result of the biexponential nature of Eq. (35). Up to 6 hours, both the absorption process [exp(—kat) and the elimination process [exp( keil)] influence the plasma concentration. After 6 hours, only the elimination process influences the plasma concentration. 

Fig. 10 Semilogarithmic plot of observed plasma concentrations (crosses) and residuals (circles) versus time for an orally administered drug absorbed by a first-order process.

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. 

Fig. 4.1. Relationship between the absorbed vivo perfusion of the human jejunum (B) (data fraction (FA) of structurally diverse sets of compiled from publications by Lennernas orally administered drugs and permeability laboratory [63, 115]). Sigmoidal relationships coefficients obtained in Caco-2 cell monolayers were obtained between FA and the (A) (data compiled from publications by permeability coefficients in both models.

Fig. 21.1. Percent sales of orally administered drugs for the 50 most sold products in US and Europe (from IMS Health 2001).

FIGURE 3.1 Absorption curve for an orally administered drug. maximum concentration A a, rate of absorption A (.. rate of elimination and A m, rate of metabolism. 

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. 

Absorption of orally administered drugs depends mainly on dissolution if the compound is poorly soluble but highly... 

Macheras P, Reppas C, Dressman JB. Biopharmaceutics of Orally Administered Drugs. 1st ed. Hemel Hempstead, Hertfordshire, UK Ellis Horwood Ltd., 1995. 

Lindenberg M, Dressman J, Kopp S. Classification of orally administered drugs on the WHO Essential Medicines list according to the BCS. Eur J Pharm Biopharm 2004 58 265-278. 

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. 

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