Abstract
Enzyme activity for demethylation processes can be estimated in vivo non-invasively by 13C-breath tests (BT). After oral intake of stable isotope labeled 13C-aminopyrine (AP) (2 mg/kg) resp. 13C-methacetin (MAC) (1,5 mg/kg) 13CO2-concentration in breath samples measured by ratio mass-spectrometry will reflect cytochrom P450 dependent AP-N-demethylation resp. P448 MAC-O-demethylation. Neonates of epileptic women exposed prenatally to anticonvulsants were studied by 13C-AP-(n=25) and 13C-MAC-BT (n=18) while 6 non-exposed newborns served as controls. Half life times of diaplacentally acquired anticonvulsants were determined in 14 resp. 7 of the exposed neonates. The 2h cumulative 13C-elimination of exposed newborns (7.1 range: 3.4-15.0 (%13C-dose) ) was significantly (p<0.005) above those of non-exposed neonates (1.7: 1.0-3.2) in 13C-AP-BT as well as in 13C-MAC-BT (18.9: 13.8-25.8 versus 9.7: 5.3-18.0) (p<0.05). In normal neonates AP-N-demethylation amounts to only 15 % of those values found in older children aged 2 y or more, while MAC-O-demethylation at that time is significantly higher (30 % of older controls).However,the intrauterine exposure to anticonvulsants will induce both demethylation processes to the same degree (60 % of older controls). Enzyme induction estimated by 13CBT did not correlate in all instances with half life time of anticonvulsants determined in the same individuum,reflecting the multiplicity of enzyme systems and selectivity of the different tests.
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Rating, D., Nau, H. & Helge, H. Enzyme induction following prenatale exposure to anticonvulsants measured by 13C-breath tests. Pediatr Res 18, 805 (1984). https://doi.org/10.1203/00006450-198408000-00080
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DOI: https://doi.org/10.1203/00006450-198408000-00080