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Disorders of the gastrointestinal system

Bioavailability is the fraction of the dose administered that reaches the systemic circulation unchanged. Sometimes, the bioavailability term is used to encompass both the rate and extent of absorption from the site of administration to the systemic circulation. For orally administered drugs, the bioavailability is affected by the amount of drug that is absorbed across the intestinal epithelium as well as first pass metabolism as the drug crosses the intestine and liver on its way to the systemic circulation. An increase or decrease in bioavailability directly impacts the oral AUC or total drug exposure. For low hepatic extraction ratio drugs, bioavailability is not affected by enzyme activity, hepatic blood flow or protein binding. In contrast, for high hepatic extraction ratio drugs, bioavailability is decreased by an increase in enzyme activity, decreased hepatic blood flow and/or a decrease in plasma protein binding. In addition to the above described changes in enzyme activity, protein binding and blood flow which can alter medication pharmacokinetics, other physiologic changes that occur during pregnancy which might influence the bioavailability of drugs include: gastric acidity, gastrointestinal transit time, and hypertrophy of duodenal villi, which can alter drug absorption

If the oral formulation of a drug has a mean bioavailability of 50%, the drug dose must be doubled to achieve the same concentrations in plasma as achieved using the IV formulation. However, the variability of the bioavailability in the population is more clinically significant than the mean. To make sure that the horse with the poorest absorption is dosed appropriately, the dose must be increased according to the lowest bioavailability, not the mean. For example, if a drug has a mean F of 50% with a range of 20% to 70%, then to achieve an exposure of 100% for all the treated horses, the dose must be multiplied by 5, not just 2. However, if this is done, the horses with an F of 70% will be overdosed by a factor of 3.5. For a drug with a narrow therapeutic window and a poor bioavailability, there may be no dose that is ideal for all horses in the population. Low bioavailability of antimicrobials and anthelmintics is a major cause of subtherapeutic dosages that promote drug resistance. Poor oral bioavailability is a major limitation of many drugs administered to horses.