Affecting Drug Absorption

For some drugS/ absorption is limited by a compound s solubility/ with dissolution being highly dependent on gastric pH. The antiretroviral agent didanosine/ for example/ is an acid-labile compound/ originally formulated as a buffered preparation to improve its bio availability. Other medications/ such as atazanavir and certain azole antifungals (particularly 

Alteration of normal gut flora has been proposed as a mechanism to explain alterations in the concentrations of several drugs, including digoxin, oral contraceptives, and warfarin, during antibiotic 

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A biologically important factor affecting drug absorption is drug metabolism or reaction coincident with diffusion across a membrane. The reaction often produces inactive or less potent products than the parent drug. It is conceivable that the reaction will also reduce the drug flux into the systemic circulation. We are interested in the effect of reaction on membrane diffusion. 

FACTORS SUCH AS CHARGE THAT AFFECT DRUG ABSORPTION, DISTRIBUTION, AND EXCRETION... 

Martinez MN, Amidon GL (2002) A mechanistic approach to understanding the factoirs affecting drug absorption A review of fundamentals. J. Clin. Pharmacol. 42 620-643. 

E. To be approved, generic formulations must exhibit the same rate and extent of absorption as the trademark compound. All of the other choices can affect drug absorption. For example, slowing gastric emptying time may increase the absorption of a... 

Absorption of drugs, which occurs mainly via passive diffusion, changes little with advancing age. The changes listed in Table 1 could potentially affect drug absorption. More important changes result from the concurrent administration of several medications. For example, antacids decrease the oral absorption of cimet-idine, and alcohol accelerates the absorption of chloral hydrate. 

In the last three decades the science and practice of biopharmaceutics has evolved from a mostly empirical study of factors that affect drug absorption to a more rigorous mechanistic study of drug absorption at the cellular level. This new understanding is providing novel opportunities in every aspect of the drug development process, such as ... 

Absorption from the Gl tract is governed by many factors. Broadly, it can be categorized into three classes physicochemical properties, biopharmaceutical factors, and physiological and pathophysiological factors (Mojaverian et al., 1985,1988 Nomeiretal., 1996). Since this chapter focuses on the pharmacokinetic perspectives, the main factors that could affect drug absorption are merely listed below, and will be discussed in detail in other chapters. 

Many physiological aspects affect drug absorption from the rectum (Table 7.1). Influential factors include the pH of the rectal contents, state of the mucus layer, volume and viscosity of rectal fluid, luminal pressure from the rectal wall on the dosage form, enzymatic and microbacterial degradation by rectal epithelium, presence of stools, and venous drainage differences within the rectosigmoid regions. 

Solutions. For oral solutions, elixirs, syrups, tinctures, or other solubilized forms, in vivo BA and/or BE can be waived [21 CFR 320.22(b) (3) (i)]. Generally, in vivo BE studies are waived for solutions on the assumptions that release of the drug substance from the drug product is self-evident and that the solutions do not contain any excipient that significantly affects drug absorption [21 CFR 320.22(b)(3) (iii) ]. However, there are certain excipients, such as sorbitol or mannitol, that can reduce the BA of drugs with low intestinal permeability in amounts sometimes used in oral liquid dosage forms. 

As well as affecting mucociliary clearance, many nasal diseases including hayfever induce inflammation in the nasal cavity and render the nasal epithelium leakier or more permeable than normal. This would be likely to affect drug absorption but not necessarily in a reproducible manner. 

Both the type of drug delivery system and the specific type of delivery device can affect drug absorption via the nasal route. The choice of delivery system depends mainly on the physiochemical properties of the drug, its desired site of action, and, more importantly, patient compliance and marketing aspects. The formulations most commonly used in nasal delivery are solutions, suspensions, gels, dry powders, and, most recently, nanoparticulate formulations. 

Welling PG. Interactions affecting drug absorption. Clin Pharmacokinet 1984 9 404-34... 

FORMULATION FACTORS AFFECTING DRUG ABSORPTION AND ABSORPTION ENHANCERS... 

Welling, P.G. Physicochemical and formulation factors affecting drug absorption. In Pharmacokinetics Processes, Mathematics, and Applications, 2nd Ed. American Chemical Society Washington, DC, 1997 88. 

Factors affecting drug absorption include formulation, disease state, food effect, and drug-drug interaction. Formulations used for oral administration include solutions, suspensions, capsules, and uncoated and coated tablets. Depending on the formulation of a drug, the absorption characteristics may differ substantially. 

Table 1 Factors affecting drug absorption from the colon Physical characteristics of drug (pkTa> degree of ionization) Colonic residence time as dictated by gastrointestinal tract motility...

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