Drug Absorption and Bioavailability

Pharmacokinetics describes drug absorption, distribution, metabolism, and excretion processes. Absorption is the rate and extent at which drugs reach the systemic circulation from the site of administration. Distribution of a drug includes all the processes that are involved from the time when the drug reaches the circulation to the time when it (or a metabolite of the drug) leaves the body. Metabolism involves all the biochemical processes that result in a chemical change to the drug compound including both the metabolism in the gut wall, the liver, and blood circulation. Excretion is the process in which the drug is eliminated from the systemic circulation into bile, urine, feces, sweat, and air (Allen, 1982). The reader is referred to authoritative texts in this area for a detailed review.

Bioavailability means the rate and extent to which the API or active moiety is absorbed from a drug product and becomes available at the site of action (Atkinson, 2001; Chiou, 2001; Toutain and Bousquet-Melou, 2004). Drug absorption plays an important role in bioavailability ( F) determination since the drug absorption contributes importantly to the time and extent that drug targets exposure to therapeutic drugs in vivo. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by the measurements intended to reflect the rate and extent to which active ingredient or active moiety becomes available at the site of action. Bioavailability can be mathematically represented by the equation: F = Fa x Fg x Fh, in which Fa is the fraction of drug absorbed, Fg is the fraction that escapes metabolism in the gastrointestinal tract, and Fh is the fraction that escapes first pass hepatic metabolism (Kwan, 1997; Sun et al., 2004). Based on the above equation, one of the main factors governing the bioavailability of a compound is the fraction of the drug absorbed.

Oral drug absorption process occurs mainly in small intestinal regions, which includes passive transcellular diffusion, carrier-mediated transport processes, paracellular transport, and endocytosis. In general, lipophilic compounds are usually absorbed by passive diffusion through the intestinal epithelium. Many hydrophilic compounds are absorbed through a carrier-mediated process, while some small hydrophilic compounds may be transported through the paracellu-lar junction. Under physiological conditions, the fastest absorption process may dominate the absorption for a particular compound (Sun et al., 2004; Cao et al., 2005).

Absorption of a compound is governed by many processes. Two fundamental parameters govern drug absorption: drug solubility and gastrointestinal permeability (Amidon et al., 1995). If both drug solubility and permeability are enhanced, there will be a great increase in the rate and extent of oral absorption. Therefore, the oral bioavailability of a drug is largely a function of its solubility characteristics in gastrointestinal fluids, absorption into the systemic circulation, and metabolic stability.

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