ABSTRACT
The phase 1 metabolites of some important drugs are not water-soluble enough or polar enough for excretion, e.g. the metabolites of aspirin, morphine and methyldopa. These, and others, undergo further enzymatic chemical processing in the liver, known as phase 2 metabolisms. The result of the first phase of drug metabolism is that the metabolite is more easily excreted via the kidneys, which are by far the most important route of drug excretion. Many drugs are excreted unchanged in the urine, and most of the rest are excreted as phase 1 or phase 2 metabolites. Excretion of drugs in breast milk is not a maternally significant route of excretion, but may be very harmful to the breastfed baby. Disruption of enterohepatic cycling explains why diarrhoea from any cause, including the therapeutic use of antibiotics, results in plasma concentrations of oestrogen inadequate to suppress ovulation. Factors affecting enterohepatic cycling, for example diarrhoea, can reduce the plasma concentration of some drugs.
