Drug Metabolism in the Newborn Rabbit

Fouts, James R.; Adamson, Richard H.

doi:10.1126/science.129.3353.897

Cited by 278 publications

(65 citation statements)

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“…VOLUME 52, 1972 • pages 733-742 more, the response of the microsomal system to these agents is a function of the stage of tissue development. Thus, earlier work had indicated that drug metabolism in fetal and neonatal tissue is low but that it increases rapidly to adult levels very shortly after birth (19,20,21,26,37) . Kato et al .…”

Section: Introductionmentioning

confidence: 99%

Ontogenetic Changes of Proteins of Endoplasmic Reticulum

Black

Bresnick

1972

The Journal of Cell Biology

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The proteins of the smooth and rough endoplasmic reticulum from fetal, immature, and adult male rats were compared after incorporation of two radioactively labeled precursors, "C-labeled amino acids and S-aminolevulinic acid 3 H by means of gel electrophoresis. The labeling patterns indicated that protein components present in two major electrophoretic bands underwent significant synthesis in fetal tissue while three actively incorporating protein bands were noted in adult tissue . Although the uptake of the amino acids-'4 C decreased for the smooth and rough elements of the endoplasmic reticulum as a whole during liver development, the qualitative patterns were not significantly different in adult and fetal livers . The over-all incorporation (disintegrations per minute per milligram protein) of the heme precursor into the smooth and rough elements also did not change with development . However, a change was noted in the distributional electrophoretic patterns with development . The estimation of molecular weight (by disc electrophoresis) and the incorporation of the heme precursor suggested the similarity of the two major protein bands to cytochrome P-450 and cytochrome b5 , components of the endoplasmic reticulum, thought to be involved in the mixed-function oxidase system . The evidence indicated that in fetal liver, at a time when the oxidase capability was low, the amino acid incorporation into these two protein groups was the same as in the adult . The incorporation of the heme moiety, however, was different, decreasing in the cytochrome b 5 region and increasing in the cytochrome P-450 region during development . These results correlate with the increase in oxidase activity associated with liver development .

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Section: Introductionmentioning

confidence: 99%

Ontogenetic Changes of Proteins of Endoplasmic Reticulum

Black

Bresnick

1972

The Journal of Cell Biology

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“…Humans have approximately 57 functional P450 enzymes, of which approximately 20 members in the CYP1, 2, 3, and 4 families are probably involved in drug metabolism. It has been known since the 1950s that P450 enzymes are not mature at birth (Fouts and Adamson, 1959); however, at that time, it was thought that there was only one or perhaps two P450 enzymes. Since the cloning of the P450 genes, ontogenic expression of some P450 genes in human livers has been reported (de Wildt et al, 1999;Koukouritaki et al, 2004;Blake et al, 2005;Leeder et al, 2005;Gaedigk et al, 2006;Hines, 2007).…”

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Three Patterns of Cytochrome P450 Gene Expression during Liver Maturation in Mice

Hart¹,

Cui²,

Klaassen³

et al. 2008

Drug Metab Dispos

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ABSTRACT:The neonatal period of liver development is an often overlooked phase of development. For instance, ontogeny of xenobioticmetabolizing enzymes can markedly affect biotransformation as the liver matures. To systematically examine the ontogenic gene expression patterns of cytochrome P450 genes (P450) in mice, the gene expression profiles of 19 xenobiotic-metabolizing P450 in Cyp1 to 4 families were determined. The mRNA levels in C57BL/6 mouse livers were quantified using branched DNA technology at the following ages: gestational day 17 (2 days before birth) and postnatal days 0, 1, 3, 5, 10, 15, 20, 30, and 45. Among the 13 P450 genes expressed in mouse livers, three distinct ontogenic expression patterns were identified by cluster analysis. Genes in group 1 (Cyp3a16 as well as 3a41b in male) were expressed in the perinatal period, but they were essentially nondetectable by 30 days of age. Genes in group 2 (Cyp2e1, 3a11, and 4a10 as well as 3a41b in female) quickly increased after birth and reached maximal expression levels by day 5. Genes in group 3 (Cyp1a2, 2a4, 2b10, 2c29, 2d22, 2f2, 3a13, and 3a25) were expressed at low levels until days 10 to 15, but they markedly increased at day 20 to a high and stable level. In conclusion, the developmental expression of P450 in mouse liver can be divided into three patterns, suggesting that different mechanisms are responsible for the expression of P450 during liver maturation.

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“…The metabolism of amidopyrine and phenacetin was similarly reduced in new-born mice. The side chain oxidation of hexobarbitone by liver homogenates from rabbits 2 to 3 weeks old was only 5 to 37% of that from adult rabbits (Fouts and Adamson, 1959): while new-born guinea-pig tissues were unable to form glycuronides (Brown and Zuelzer, 1958). Indeed there is much evidence that the concentrations of various enzymes in mammals are low at birth and increase during the first days of life (Potter, Schneider and Liebl, 1945;Reem and Kretchmer, 1957 ;Dawkins, 1959).…”

Section: Discussionmentioning

confidence: 99%

Anaesthesia in New‐born Animals

Weatherall

1960

British Journal of Pharmacology and Chemotherapy

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Pentobarbitone was more toxic to new-born than to adult rabbits and rats, produced a longer loss of righting reflex in new-born animals but did not anaesthetize them effectively in less than toxic doses. Urethane did not anaesthetize new-born animals in doses which anaesthetized adults. Ether produced loss of righting reflex at lower concentrations for new-born than for adults, but the new-born animals became anaesthetized more slowly.

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Drug Metabolism in the Newborn Rabbit

Cited by 278 publications

References 1 publication

Ontogenetic Changes of Proteins of Endoplasmic Reticulum

Ontogenetic Changes of Proteins of Endoplasmic Reticulum

Three Patterns of Cytochrome P450 Gene Expression during Liver Maturation in Mice

Anaesthesia in New‐born Animals

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