02.03.4 First Pass Metabolism and Bioavailability

The relationship between first pass metabolism and bioavailability has been discussed previously (Chapter 1), and is only discussed briefly here. Drugs with extensive first pass liver metabolism have poor bioavailability after oral administration. An example of a drug that undergoes extensive first pass liver metabolism is glyceryl trinitrate (nitroglycerin), which is used in the treatment of angina. Due to this metabolism, glyceryl trinitrate has to be administered by other routes of administration. Glyceryl trinitrate is used sublingually.

When drugs have considerable first pass liver metabolism, but a proportion still gets to the systemic circulation, it may be possible to increase the dose of drug, to increase the amount of drug that reaches the systemic circulation. This is the case with the painkillers morphine and pethidine. Large doses of the anti-Parkinson’s drug L-dopa are also required to produce effective plasma levels of L-dopa.

In liver disease, the metabolism of certain drugs may be inhibited, increasing bioavailability. With increased bioavailability, there will be increased effects of a drug. Indeed the plasma levels maybe increased enough to cause toxic effects. Thus, in liver disease, it may be necessary to decrease the doses of drugs metabolised by the liver.