Abstract
14C aminopyrine is widely used as a dynamic liver function test measuring 14CO2 produced by hepatic demethylation
of the drug. In the standard test a single breath sample is collected and assumed to represent average production of 14CO.
We have found that this method underestimates the true rate of excretion and is insensitive to changes in microsomal
activity. By standard testing the % dose excreted was unaffected by induction with glutethimide (change in dose excreted in
two hours =-3 0%, P>0-50), although antipyrine clearance (P<0-005) and dglucaric acid excretion (P<0-02) rose significantly. By contrast repeated sampling gave an area under the two hour
14C02 specific activity curve which rose significantly (change in dose excreted in two hours = +25-6%, P<0-02).
Sensitivity of testing can be further increased by monitoring endogenous CO2 production. Induced individuals have an
early high production of l4CO, followed by a rapid fall and an actual reduction in the area under the 24 hour 14CO2 curve. This
suggests that, although their capacity to demethylate is enhanced, substrate is also removed rapidly by alternative pathways. It follows that the slope of the "4CO2 disappearance curve is not a pure measure of demethylation rate, but reflects overall removal of "IC aminopyrine from its site of demethylation in the hepatocyte. This test is likely to have greater potential as a
refined liver function test than has been realised.
of the drug. In the standard test a single breath sample is collected and assumed to represent average production of 14CO.
We have found that this method underestimates the true rate of excretion and is insensitive to changes in microsomal
activity. By standard testing the % dose excreted was unaffected by induction with glutethimide (change in dose excreted in
two hours =-3 0%, P>0-50), although antipyrine clearance (P<0-005) and dglucaric acid excretion (P<0-02) rose significantly. By contrast repeated sampling gave an area under the two hour
14C02 specific activity curve which rose significantly (change in dose excreted in two hours = +25-6%, P<0-02).
Sensitivity of testing can be further increased by monitoring endogenous CO2 production. Induced individuals have an
early high production of l4CO, followed by a rapid fall and an actual reduction in the area under the 24 hour 14CO2 curve. This
suggests that, although their capacity to demethylate is enhanced, substrate is also removed rapidly by alternative pathways. It follows that the slope of the "4CO2 disappearance curve is not a pure measure of demethylation rate, but reflects overall removal of "IC aminopyrine from its site of demethylation in the hepatocyte. This test is likely to have greater potential as a
refined liver function test than has been realised.
| Original language | English |
|---|---|
| Article number | T38 |
| Pages (from-to) | A929 |
| Journal | Gut |
| Volume | 20 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 1979 |
| Externally published | Yes |