[Use of the labelling of drugs with stable isotopes in clinical pharmacology in children].
There are only few studies available in the literature, using drugs labelled with stable isotopes in pediatric clinical pharmacology. However, the stable isotope methods are of great potential interest. These sensitive methods allow to quantitate drugs in small volumes of biological fluid with great specificity. They are innocuous and allow in vivo drug metabolic studies. Using 1-3 15N, 2 13C labelled theophylline, it has been possible to demonstrate N7-theophylline methylation into caffeine in premature neonates while this metabolic pathway is virtually not existent in adults. Stable isotope techniques allow to study intraindividual changes in kinetic parameters of drugs during maintenance therapy without discontinuing the drug. For instance, auto-induction of carbamazepine metabolism was demonstrated in children using stable isotope-labelled carbamazepine in serial pharmacokinetic studies during maintenance therapy. They also make bioavailability studies possible in children. These methods make possible new non invasive studies like CO2 breath test. Using 1-3-7 13C-caffeine we demonstrated the feasibility of the CO2 breath test in young infants and described the maturation of the N-demethylation pathway for caffeine. The correlation between the rate of 13C-CO2 elimination and caffeine plasma clearance indicates that the CO2 breath test is a non invasive method useful for measuring caffeine N-demethylation and that this test might theoretically be used for monitoring caffeine treatment.
Pons
G
G
Département de Pharmacologie Clinique Périnatale et Pédiatrique, Hôpital Saint-Vincent-de-Paul, Paris.
Rey
E
E
Badoual
J
J
Olive
G
G
D002648:Child; D006801:Humans; D007553:Isotope Labeling; D010372:Pediatrics; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010599:Pharmacokinetics
D004364:Pharmaceutical Preparations
Utilisation du marquage des médicaments par les isotopes stables en pharmacologie clinique chez l'enfant.