Drug metabolism differs in children and adults
Specific differences between children and adults in the types and levels of enzymes that metabolise drugs have now been identified by researchers.
Ronald Hines, professor of paediatrics at the Medical College of Wisconsin,
presented data at the American
Association for the Advancement of Science annual meeting in St Louis, Missouri, last week. The data were obtained
through analysis of samples from a tissue bank of human liver cells representing
ages from eight weeks’ gestation to 18 years.
The researchers found that, at one or two years old, children have only
20 to 50 per cent of adult levels of the oxidative enzyme CYP3A4, with
a gradual increase observed until adult levels are reached at 18 years.
In contrast, they say that 50 per cent of children have adult levels
of CYP2C9 at or near birth. Of the conjugating enzymes studied, SULT2A1
is low or absent during the first trimester, is highly variable in the
first four months of life and increases gradually to adult levels by
the age of one year. In addition, SULT1A1 is constant throughout development
and SULT1E1 levels are five times higher than adult levels throughout
the first trimester and decline steadily after that.
“The dramatic changes observed in enzyme expression must be considered
when examining issues of drug effectiveness and safety during early life
stages,” said Dr Hines. He added that additional studies are needed
to understand how these changes are regulated in order to better predict
drug responses in children. |
The
Pharmaceutical Journal
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