Validation of 13CO2 breath analysis as a measurement of demethylation of stable isotope labeled aminopyrine in man

Abstract

Interval sampling of expired breath as a simple, non-invasive assessment of the effect of liver disease upon hepatic microsomal drug metabolism, has been demonstrated with [14C]dimethylaminoantipyrine (aminopyrine). In order to eliminate radiation risk we have validated the use of aminopyrine labeled with the stable, non-radioactive isotope 13C. Simultaneous oral administration of both [14C]- and [13C]aminopyrine to five adult subjects without liver disease as well as five patients with known liver disease, resulted in the excretion of label at nearly identical rates in both individual time collections (r = 0.94) as well as cumulative excretion for three hours (r = 0.97). An oral dose of 2-mg/kg of [13C]aminopyrine resulted in rates of production of 13CO2 significantly greater than baseline variations in 13CO2 production in the fasting, resting subject. Measurements of a single peak value at one half hour correlated closely with the determination of cumulative appearance over three hours (r = 0.96). A consistent reproducible increase in the peak production of 13CO2 was observed when five patients received phenobarbital. Stable isotope labeled aminopyrine may be used to detect the effects of disease and treatment upon hepatic N-demethylation activity in human subjects without incurring any risk from radiation. Furthermore, the availability of another isotopic carbon label should make possible the study of direct drug-drug interaction utilizing CO2 analysis. © 1978.