Elimination is the irreversible loss of drug from the body. It can occur by two processes. Either the drug is excreted chemically unchanged, or it is metabolised from one chemical entity into another and then removed. The main routes of elimination are the kidneys, the hepatobiliary system (some drugs are excreted in the bile or in faeces) and the lungs.


Drug metabolism occurs primarily in the liver, by the cytochrome P450 (CYP450) enzyme system. When a drug is absorbed through the GI tract, it often undergoes first-pass metabolism. This is where the absorbed drug passes through the liver before being distributed throughout the rest of the body; and whilst in the liver, it is metabolised. This process can either activate a drug, as is the case with valaciclovir, or form an inactive metabolite, as with the opioid analgesics. Some metabolites may be toxic and lead to adverse effects. If a drug is heavily metabolised in the liver, it can lead to poor oral bioavailablity, resulting in higher doses being required. Some drugs can inhibit or induce CYP450 enzymes, leading to drug-drug interactions. For example, ritonavir is a potent inhibitor of cytochrome isoenzyme 3A4; thus it can greatly affect the bioavail-ability of other drugs, such as sildenafil.


The majority of drugs are excreted by the kidneys either unchanged or as metabolites; however, protein-bound drugs will not be renally excreted. In patients with impaired renal function, drug toxicity can sometimes develop if doses are not adjusted. In some cases, the creatinine clearance (CrCl) can be calculated for an individual, and can be used to work out the dosing of their drug treatment. Clearance is defined as the volume of plasma containing an amount of substance that is eliminated from the body in a unit of time (ml/min). Generally, the smaller the size of the drug molecule, the more likely it is to be excreted by the kidneys. The liver eliminates some drugs altogether.

However, it is usually much more difficult to gauge liver function, and hence the dosing of drugs is not as straightforward as it otherwise might be.

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