Enzyme induction in neonates after fetal exposure to antiepileptic drugs
The /sup 13/C-AP breath test is shown to be a convenient, noninvasive method to monitor velocity and capacity of P450-dependent AP N-demethylation in infancy and childhood. According to /sup 13/C-AP breath tests, neonates have a very low capacity to eliminate /sup 13/CO/sub 2/, which is only 15 to 21% of the activity in adults. During the first year of life AP N-demethylation increases to reach its maximum at about 2 years; afterwards a slight decrease occurs. In 25 neonates exposed prenatally to different antiepileptic drugs /sup 13/C-AP breath test was efficiently used to prove that cytochrome AP N-demethylation was considerably stimulated. After primidone/phenobarbitone, especially in combination with phenytoin, /sup 13/C elimination reaches and even surpasses the range for older children. Valproate exposure during fetal life is not consistently followed by a significant increase in AP N-demethylation. The enzyme induction demonstrated by /sup 13/C-AP breath test was often accompanied by accelerated metabolic clearance and shortened half-life times of transplacentally acquired antiepileptic drugs. There was good agreement between /sup 13/C-AP breath tests and pharmacokinetic data for primidone/phenobarbitone but not for phenytoin. In contrast, in the case of phenytoin exposure during pregnancy the pharmacokinetic parameters and the /sup 13/C breath test data will transport very different informations about enzyme induction in these neonates.
- Research Organization:
- Free Univ. of Berlin, Federal Republic of Germany
- OSTI ID:
- 6305973
- Journal Information:
- Pediatr. Pharmacol.; (United States), Vol. 3:3-4
- Country of Publication:
- United States
- Language:
- English
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ANTICONVULSANTS
BIOLOGICAL EFFECTS
PRENATAL EXPOSURE
CARBON 13
EXHALATION
CARBON DIOXIDE
CARBON-CARBON LYASES
CHEMICAL ACTIVATION
AMINES
INFANTS
PHARMACOLOGY
AGE GROUPS
CARBON COMPOUNDS
CARBON ISOTOPES
CARBON OXIDES
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHALCOGENIDES
CHILDREN
CLEARANCE
DRUGS
ENZYMES
EVEN-ODD NUCLEI
EXCRETION
ISOTOPES
LIGHT NUCLEI
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NUCLEI
ORGANIC COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
STABLE ISOTOPES
551001* - Physiological Systems- Tracer Techniques