PHAR 4634 - Chapter 17 Page 5 Previous Chapter | Previous Page | Index | Next Page | Next Chapter

Systemic availability

Even if we can assume that a drug is completely absorbed across the G-I tract, a proportion of the dose may be eliminated by the liver before reaching the systemic circulation because of the anatomical arrangement of the portal circulation. This pre-systemic or first-pass elimination can be determined from the extraction ratio, E, such that the fraction of the dose that is available to the central circulation is 1-E. This 1-E value becomes the maximum availability possible before allowing for reduced product performance.

For drugs which are extensively metabolized, first pass metabolism can be quite important. It means that higher doses must be given orally compared with parenteral administration.

for example morphine p.o. 30 mg cf. IV. 5 mg

lidocaine not active p.o.

In liver disease there is potential for changing the systemic availability of high extraction drugs and thereby affecting steady state concentrations.

If liver disease causes a modest reduction in the extraction ratio, from for example 0.95 to 0.9, the fraction of the orally administered drug reaching the systemic circulation (1-E) will be doubled. One of the consequences of the pathogenesis of chronic liver disease is the development of porta-systemic shunts that may carry drug absorbed from the G-I tract through the mesenteric veins directly into the systemic circulation. Thus in a disease where biochemical hepatic function is relatively well maintained (e.g., schistosomiasis), oral treatment with high clearance drugs such as morphine or propranolol can lead to high blood levels and an increase in adverse drug effects. For example, 30 mg morphine orally may act like 30 mg IV. and lead to over dosage with respiratory depression.

Pharmacokinetics of drugs in patients with liver disease.

Second Semester Exam 1995 (nm)

This page was last modified: 12 February 2001

Copyright 2001 David W.A. Bourne

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