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Drug absorption after oral administration has two major components: absorption rate and bioavailability. Absorption rate is controlled partially by the physicochemical characteristics of the drug but in many cases is modified by the formulation. A reduction in absorption rate can lead to a smoother concentration–time profile with a lower potential for concentration‐dependent adverse effects and may allow less frequent dosing.

Bioavailability is the term used to describe the fraction of the oral dose that is absorbed into the systemic circulation. It can range from 0 to 100% and depends on a number of physicochemical and clinical factors. Low bioavailability may occur if the drug has low solubility or is destroyed by the acid in the stomach. Changing the formulation can affect the bioavailability of a drug and it can also be altered by food or the co‐administration of other drugs. For example, antacids can reduce the absorption of quinolone antibiotics, such as ciprofloxacin, by binding them in the gut. Other factors influencing bioavailability include metabolism by gut flora, the intestinal wall or the liver.

First‐pass metabolism refers to metabolism of a drug that occurs en route from the gut lumen to the systemic circulation. For the majority of drugs given orally, absorption occurs across the portion of gastrointestinal epithelium that is drained by veins forming part of the hepatoportal system. Consequently, even if they are well absorbed, drugs must pass through the liver before reaching the systemic circulation. For drugs that are susceptible to extensive hepatic metabolism, a substantial proportion of an orally administered dose can be metabolised before it ever reaches its site of pharmacological action, e.g. insulin metabolism in the gut lumen is so extensive that it renders oral therapy impossible. Other drugs which undergo extensive hepatic metabolism include propranolol, lidocaine and morphine.

First‐pass metabolism has several clinical implications:

1 The appropriate route has to be selected for a drug in order to obtain its clinical effect

2 It accounts for the variability in drug bioavailability between individuals

3 Liver disease can reduce the first‐pass effect and result in an increase in bioavailability. This is discussed in greater detail later in this section.