Pharmacokinetics of benzodiazepines and psychostimulants in children.
The pharmacokinetics of benzodiazepines and psychostimulants are reviewed and an overview of the kinetic principles relevant to the utilization of these drugs in infancy and childhood is provided. Newborns and premature infants can metabolize and eliminate diazepam, although the parent drug has a longer half-life and decreased rate of biotransformation to its primary metabolites than in older children and adults. The newborn's capacity to carry on metabolic processes involved in the biotransformation of diazepam, including hydroxylation, demethylation, and glucuronide conjugation, is also limited before 5 months of age; after this time hepatic enzymes develop to adult capacity. Kinetic studies of psychostimulants in childhood indicate that methylphenidate is metabolized in the child as it is in the adult. The drug appears to be rapidly metabolized to ritalinic acid and the half-life seems to be relatively short. Volumes of distribution appear to be relatively large, suggesting extensive distribution of the drug to body tissues. Neither diazepam nor methylphenidate is without the potential for toxicity, which increases with dosage. The authors conclude that advancements in the technical capacity for obtaining and analyzing microsamples of blood as well as the use of noninvasive urinary studies will make future research in children possible.
D000293:Adolescent; D000328:Adult; D014151:Anti-Anxiety Agents / Q000097:blood*; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood; D001711:Biotransformation; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D003975:Diazepam / Q000097:blood; D004827:Epilepsy / Q000097:blood; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007700:Kinetics; D008297:Male; D008774:Methylphenidate / Q000097:blood*; D003708:Nordazepam / Q000097:blood
D014151:Anti-Anxiety Agents; D008774:Methylphenidate; D003708:Nordazepam; D003975:Diazepam