Feb 19 2006
A new study has provided the strongest and most comprehensive evidence yet of the difference between how adults and infants and children process drugs.
The researchers say that when children are given smaller doses of drugs which have only been tested on adults they are at greater risk of harmful side effects.
Apparently most drugs given to newborn babies, and 50 per cent of those given to children of all ages, have not been tested to ensure that they are appropriate for them.
Previous studies show that under-18s suffer up to three times more side effects from drugs than adults.
This say the researchers is because the proportions of proteins in the body that control their effectiveness change as humans grow older.
The study by a team at the Children's Research Institute, Wisconsin, reveals quite surprising metabolic differences in how drugs are processed by the young and by adults, and the major changes occurring during human development in the types and levels of enzymes responsible for the disposition of drugs and environmental chemicals.
These enzymes they say are able to inactivate drugs, activate them, or do both, depending on the compound and the number of enzymes involved.
They also say some environmental toxicants are inactivated and some are activated, depending on the chemistry of the compound, and sometimes, the dose.
The study was led by Ronald N. Hines, Ph.D., professor of pediatrics and of pharmacology and toxicology, and associate director of the Children's Research Institute, Children's Hospital, which is a major teaching affiliate of the Medical College.
In the study the researchers used tissue samples from 240 children aged from eight weeks to 18 years old to study the levels of different enzymes compared with those in adults.
They found that by the time a child reached age one or two years, it has only 20 to 50 per cent of the adult proportion of a vital enzyme known as CYP3A4 and that the quantity increases gradually until the youngster reaches 18.
Enzyme levels were found to vary differently in children aged between three and six months, suggesting the effects of different drugs could vary from child to child during that period.
The study found that some enzymes known to share regulatory mechanisms in adults appear to use different regulatory mechanisms during development.
Dr. Hines says these dramatic changes need to be considered for drug effectiveness and safety during early life stages as they have the potential to prevent the treatment from working or cause overdoses.
Hines says more research is needed to understand how these dramatic changes are regulated, and how they differ among individuals, in order to better predict drug and toxicant responses in children.
Dr. Hines concludes that the application of this and similar information could help predict an individual child's likelihood of effective drug treatment or susceptibility to an unfavorable drug reaction.
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