Drug Metabolism in the Neonate
J. Ara b Neonatal Forum 2005; 2: 1-4
Drug Metabolism in the Neonate
Imti Choonara
Academic Division of Child Health, University of Nottingham, Clinical Sciences Wing
The Medical School, Derbyshire Children ’s Hospital, UK
_____________________________________________________________________________________________
Abstract
The newborn infant has a reduced capacity for drug metab olism in comp arison with infants and children. This is more marked in the preterm neonate. Altered drug metabolism may predispose the neonate to a greater risk of drug toxicity. Neonates usually require smaller doses of drugs administered less frequently than infants and children.
Keywords: Drug metabolism – neonate – caffeine – midazolam – morphine – paracetamol
The importance of drug metabolism in the neonate is
Different developmental patterns have been identified illustrated by the chloramphenicol tragedy. for CYPs involving activity in the fetal liver
1
Newborn infants who received chloramphenicol
(CYP3A7), minimal activity in the fetal liver but with developed the grey baby syndrome. This involved rapid increase hours after birth (CYP2D6 and cardiovascular collapse, irregular respiration and
CYP2E1) and development in infancy (CYP1A2).
3– 6 subsequent death. Recognition that the newborn
For many drugs weight corrected clearance values are infant was unable to metabolise chloramphenicol as often low at birth but then increase rapidly reaching a effectively as adults resulted in a reduction in the maximum by 2 years of age. total daily dosage from 100 mg/kg to 50 mg/kg. Use of the lower dosage did not result in development of
CYP3A4
the grey baby syndrome.
The CYP3A subfamily is the most abundantly expressed CYP subfamily in the human adult and
The biological purpose of drug metabolism is to newborn liver. Moreover, this subfamily is involved conv ert lipophilic (fat soluble) comp ounds into more in the metabolism of more than h alf of all
Drug Metabolism in the Neonate
Imti Choonara
Academic Division of Child Health, University of Nottingham, Clinical Sciences Wing
The Medical School, Derbyshire Children ’s Hospital, UK
_____________________________________________________________________________________________
Abstract
The newborn infant has a reduced capacity for drug metab olism in comp arison with infants and children. This is more marked in the preterm neonate. Altered drug metabolism may predispose the neonate to a greater risk of drug toxicity. Neonates usually require smaller doses of drugs administered less frequently than infants and children.
Keywords: Drug metabolism – neonate – caffeine – midazolam – morphine – paracetamol
The importance of drug metabolism in the neonate is
Different developmental patterns have been identified illustrated by the chloramphenicol tragedy. for CYPs involving activity in the fetal liver
1
Newborn infants who received chloramphenicol
(CYP3A7), minimal activity in the fetal liver but with developed the grey baby syndrome. This involved rapid increase hours after birth (CYP2D6 and cardiovascular collapse, irregular respiration and
CYP2E1) and development in infancy (CYP1A2).
3– 6 subsequent death. Recognition that the newborn
For many drugs weight corrected clearance values are infant was unable to metabolise chloramphenicol as often low at birth but then increase rapidly reaching a effectively as adults resulted in a reduction in the maximum by 2 years of age. total daily dosage from 100 mg/kg to 50 mg/kg. Use of the lower dosage did not result in development of
CYP3A4
the grey baby syndrome.
The CYP3A subfamily is the most abundantly expressed CYP subfamily in the human adult and
The biological purpose of drug metabolism is to newborn liver. Moreover, this subfamily is involved conv ert lipophilic (fat soluble) comp ounds into more in the metabolism of more than h alf of all