Читать книгу Biopharmaceutics - Группа авторов - Страница 23

The absorption of a drug at the administration site is a complex interplay between the physicochemical characteristics of the drug and the physiology of the surrounding tissues.

The drug absorption through the gastrointestinal tract, for instance, is a function of drug's solubility (Chapter 4), its dissolution (Chapter 6) within the gastrointestinal milieu and drug's permeability across the gastrointestinal mucosa (Chapter 5) taking into account the complex gastrointestinal anatomy and physiology (Chapter 11).

The fraction of the administered dose of a drug that reaches the systemic circulation is termed the Bioavailability (F) which is a function of the fraction that permeates through the gastrointestinal mucosa (f_a), the fraction that survives gut‐wall metabolism during absorption (f_g) and the fraction which escapes the hepatic metabolism (f_h) when it passes through the liver. Figure 2.4 summarises various factors associated with drug absorption through the gastrointestinal tract. The fraction absorbed (f_a) from the gastrointestinal tract is an interplay between physicochemical properties of the drug, its solubility and dissolution rate within the gastrointestinal luminal fluids and its stability in the gastrointestinal milieu (acidic/basic pH, the digestive enzymes, and the interaction with food and its digestive products). The fraction absorbed also depends on a drug's ability to cross the gastrointestinal absorptive barrier which in turn also depends on its physicochemical characteristics, lipophilicity, the partition coefficient and its susceptibility to various influx or efflux transporters present within gastrointestinal absorptive cells. The absorption of most of the drugs administered into the gastrointestinal tract, is, therefore, a complex phenomenon; hence, the oral bioavailability (F) is rarely equal to 1 (or 100%). In contrast, if the drug was administered into the blood circulation directly, such as intravenously (injected into the veins), it bypasses the absorption barriers and entirety of the administered dose is available in the systemic circulation, hence bioavailability (F) is 1.

The science of biopharmaceutics is invaluable to understand the complex interplay between physicochemical properties of the drug and gastrointestinal physiology to develop innovative formulations and drug delivery systems (Chapter 8) to improve the drug absorption and bioavailability through various routes of administration.

Figure 2.4 Physicochemical and physiological factors affecting the absorption of the drug from the gastrointestinal tract following oral administration.