A Mechanistic Approach to Understanding the Factors Affecting Drug Absorption: A Review of Fundamentals

Abstract

This article provides an overview of the patient-specific and drug-specific variables that can affect drug absorption following oral product administration. The oral absorption of any chemical entity reflects a complex spectrum of events. Factors influencing product bioavailability include drug solubility, permeability, and the rate of in vivo dissolution. In this regard, the Biopharmaceutics Classification System has proven to be an important tool for predicting compounds likely to be associated with bioavailability problems. It also helps in identifying those factors that may alter the rate and extent of drug absorption. Product bioavailability can also be markedly influenced by patient attributes such as the integrity of the gastrointestinal tract, physiological status, site of drug absorption, membrane transporters, presystemic drug metabolism (intrinsic variables), and extrinsic variables such as the effect of food or concomitant medication. Through an awareness of a drug's physicochemical properties and the physiological processes affecting drug absorption, the skilled pharmaceutical scientist can develop formulations that will maximize product availability. By appreciating the potential impact of patient physiological status, phenotype, age, gender, and lifestyle, dosing regimens can be tailored to better meet the needs of the individual patient.

Modelling dimercaptosuccinic acid (DMSA) plasma kinetics in humans

“…These lag times vary within and between individuals, due to possible differences in upper gastrointestinal motility, fat content of food, or individual absorption characteristics. [25] Furthermore, in clinical practice, when patients are treated with chelation, detailed information regarding the exact times of meals and their contents is unavailable. So, its applicability in chelation therapy is questionable.…”

Bioavailability of oral drug formulations and methods for its improvement

“…Создана "Биофармацевтическая классификационная система" (BCS) -важный инструмент для предсказания кишечной абсорбции лекарства [1,3]. В основе её -система классификации лекарств по растворимости и проницаемости, согласно которой выделяют 4 класса веществ, в зависимости от их комбинаций.…”

“…При низкой растворимости её можно повышать, например, путем введения в лекарственную форму поверхностно-активных веществ. При хорошей растворимости наибольший эффект имеет снижение размера частиц, улучшающее абсорбцию за счёт увеличения площади поверхности и возможности выхода лекарства [1].…”

“…По мере продвижения в тонком кишечнике (в течение 2-3 часов) лекарство подвергается действию панкреатических, в том числе липолитических, ферментов, при рН 6-7, а также жёлчных кислот, оказывающих микроэмульгирующее действие. При этом могут высвобождаться молекулы лекарства, растворяясь в кишечной среде и всасываясь в стенку кишечника: в основном через энтероциты [1], и, в гораздо меньшей степени, через плотные контакты между ними [6] или клетки лимфоидной ткани [7].…”

Human colon adenocarcinoma HT-29 cell: Electrochemistry and nicotine stimulation

“…In aqueous solution, the four polar groups will be highly solvated with water molecules. In order to cross the cell membrane, these water molecules have to be "stripped away" and this involves energy [20]. Following an appropriate cell stimulation (which provokes a Ca 2+ entry or increase) and multiple protein-protein interactions, that is, the formation of soluble N-ethylmaleimide sensitive fusion protein attachment receptors (SNAREs) -vesicle-associated membrane proteins (VAMPs) complexes, the intracellular epinephrine content is released to the extracellular medium [21,22,23].…”