Absorption
Drug absorption is an important process in drug pharmacokinetics. The route of administration is an important factor in determining the rate and extent of absorption. Routes of administration can include oral, rectal, ocular, inhalation through the nose or mouth, absorption through the skin and other body surfaces, and injection into muscle or veins, etc. All of these routes have different rates and extents of absorption. Most drugs are administered orally, and hence an understanding of the mechanism of absorption by this route is most important for the toxicologist.
Absorption from the gastrointestinal tract Drugs are usually absorbed either by passive diffusion of the un-ionised drug or by active transport. Passive diffusion is by far the most common mechanism. Absorption is possible throughout the gastrointestinal tract, from stomach to rectum, although the major site is the upper small intestine. This has high peristalsis, a high surface area (200 m2), high blood flow and optimal pH (pH 5–7) for the absorption of most drugs, all of which result in a high absorption rate. Drug absorption tends to be much less rapid from other parts of the gastrointestinal tract.
Some drugs are absorbed to a small extent in the stomach, although these are largely acidic drugs that are un-ionised in the low pH (pH 1–3) environment in this organ. These drugs include aspirin, nonsteroidal anti-inflammatory drugs and some angiotensin-converting enzyme inhibitors. Absorption also occurs if drugs are given rectally as suppositories. In this situation absorption is usually less efficient than following oral administration. For example, oxycodone suppositories require a higher dose to achieve the desired response than oxycodone by oral administration.
Absorption of ionised drugs and poisons also occurs. For example, paraquat is highly ionised but appears to be absorbed slowly from the gastrointestinal tract throughout its length and over a considerable period of time from the moment of ingestion. Poisoning with orally active drugs can be treated effectively by the prompt administration of an oral adsorbent, such as activated charcoal, which prevents further absorption of the drug. This is only effective if given less than 2 h after ingestion of the drug, so that the drug has not passed too far down the gastrointestinal tract for the charcoal to gain contact with it.
Absorption from other sites Absorption through the lungs occurs for substances that are smoked or inhaled, such as smoked cocaine, heroin, tetrahydrocannabinol (THC) from cannabis, drugs such as salbutamol from inhalers, and volatile substances that are abused such as butane and toluene. The lungs are an efficient organ for the transport of a drug from the air into the blood supply, such that the rate of absorption approaches that of intravenous injection. Absorption of drugs through mucous membranes and skin is also common. This includes nasal insufflation of cocaine (‘snorting’), sublingual and buccal absorption of buprenorphine and nitroglycerine-like vasodilators, as well as absorption of drugs through skin patches (e.g. oestrogens, fentanyl, nicotine, etc.). Less commonly, toxicologists also encounter the vaginal and ocular absorption of drugs. The rate of absorption can vary significantly from one site to another. Sublingual absorption is very rapid, with drug effects noticeable within minutes, while drugs are absorbed relatively slowly through the skin.
Drugs injected into the spinal canal and into muscle or surface tissues (intramuscular, intraperitoneal) usually exhibit relatively rapid absorption. However, absorption from an intra muscular injection can be slow if the site of injection is perfused poorly by the blood supply and if the site is very fatty. Drugs that are administered to bypass the gastrointestinal tract will not be subject to first-pass metabolism . These drugs, therefore, show higher bioavailability than the same drug delivered through the gastrointestinal tract.
