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    Metabolism

    Biotransformation of drugs occurs mainly in the liver, but also in the kidney, lung, intestine, blood and adrenal. Drug-metabolising enzymes are deficient in neonates or have a low activity. Two groups of biotransforming enzymes exist in the liver: phase 1 reactions such as oxidation, reduction and hydrolysis, and phase 2 reactions like conjugations (glucuronidation and sulphation). Later, between the age of 6 months and puberty, oxidative P450 enzymes have a two times higher activity than in adults. During puberty, the activity of these enzymes decreases towards normal adult levels.

     

     

     

    Enzymes involved in glucuronidation, sulphation and acetylation reach their maturity at 3 or 4 years of age. Due to the different activities of the enzyme groups, the biotransformation of drugs can vary a lot at diverse ages.

    Example:

    • increased toxicity of chloramphenicol in neonates due to low glucuronidase activity.
    1

    Most metabolic activity in neonates is reduced.

    2

    The metabolic rate of a drug for a neonate and a small child of 3 years of age can vary greatly.

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