Oral drug absorption process

Figure 2.1 Oral drag absorption process from the gastrointestinal tract (GIT). Schematic depicting the three major processes (/a, / and /h) affecting absorption of drug from the site of administration to the systemic circulation, that is oral bioavailability, /a- fg, and /h can be estimated from the general relationship provided in Eq. 2.3 ...

Figure 21.1 Schematic representation of the main processes involved in oral drug absorption.

Yu LX, Gatlin L, Amidon G (2000) Predicting oral drug absorption in humans. In Amidon GL, Lee PI, Topp EM (ed.) Transport processes in pharmaceutical systems. Marcel Dekker, New York, pp 377-409. 

These models assume that oral drug absorption takes place under equilibrium conditions. Spatial or temporal aspects of the drug dissolution, transit and uptake and the relevant physiological processes in the gastrointestinal tract are not taken into account. Only drug-related properties are considered as the key parameters controlling the absorption process. 

Although the AP concept is a useful indicator of oral drug absorption, its qualitative nature does not allow the derivation of an estimate for Fa. A quantitative version of Fa as a function of AP was published in 1989. It was based on the equilibrium considerations used for the derivation of AP and the fundamental physicochemical properties in (6.2) with the implied competing intestinal absorption and nonabsorption processes [158]. This quantitative AP concept relies on (6.3), where a nonlogarithmic expression for AP is used ... 

Agoram B, Woltosz W, and Bolger M. Predicting the Impact of Physiological and Biochemical Processes on Oral Drug Absorption. Adv DrugDeliv Rev 200 50 S41-S67. 

Provided that metabolism and active transport systems are not the dominating factors for the drug absorption process, there are - in general terms - two factors that fairly well characterize the oral absorption the solubility in combination with the permeability throngh membranes. Consequently, four classes of substances have been defined by Amidon G. et al. ... 

Oral drug absorption is often described as a first-order mechanism, and through compartmental modeling, oral absorption is represented by the first-order absorption rate constant, ka (per time unit). Although it is not used in the current example, inclusion of lag time may be needed to better describe absorption processes. The kinetics of drug amount in the plasma following a first-order absorption process is described by a system of differential equations, as follows ... 

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. 

Usually, an increase in Cg that would affect the dissolution rate would occur only when another process, such as membrane transport or stomach emptying, becomes the rate-limiting step in drug absorption. As a general rule pharmacists should advise patients to take their oral medications with a full glass of water to ensure that dissolution occurs under optimal conditions. 

Although, the pH-partition hypothesis has not been found to be universally applicable, it has resulted in the recognition of the important contribution of GI pH to permeability and to the dissolution rate of solid dosage forms. This theory does not consider the solubility of the drug, which is a critical physicochemical parameter in the oral absorption process. Dressman et al. [34] developed an absorption potential concept that takes the two parameters into account. The absorption potential is defined as... 

The barriers confronting oral delivery of a drug molecule are summarized in Fig. 13.1. During the absorption process, the drug must cross the enterocyte cell apical... 

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