Cytochrome P450 3A

Wildt, Saskia N. de; Kearns, G. L.; Leeder, J. Steven; Anker, Johannes N. van den

doi:10.2165/00003088-199937060-00004

Cited by 496 publications

(97 citation statements)

References 131 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with the ndings of another study, 10) CYP3A4 mRNA levels in the fetal liver were about 0.1 times lower than in the adult liver. The results for the CYP3A subfamily in the fetal liver and in adult organs such as the liver, small intestine, kidney, and lung are also consistent with the data reported by Raunio et al, 11) Zhang et al, 12) Lacroix et al, 10) and De Wildt et al 13) CYP2E1 showed the highest level of mRNA expression in the adult liver, and consistent with the ndings of other studies, 14,15) CYP2E1 mRNA levels were about 20 times higher than those of CYP3A4 in the adult liver. CYP2A6 showed the second highest level of mRNA expression in the adult liver.…”

Section: Resultssupporting

confidence: 90%

Tissue Distribution of mRNA Expression of Human Cytochrome P450 Isoforms Assessedby High-Sensitivity Real-Time Reverse Transcription PCR

et al. 2003

View full text Add to dashboard Cite

Pairs of forward and reverse primers and TaqMan probes specic to each human cytochrome P450 isoform were prepared. Analysis of the mRNA level of each CYP isoform in total RNA from pooled specimens of various human or gans was performed by realtime reverse transcription PCR using an ABI PRISM 7700 sequence detector system. The ex pression of CYP3A4 mRNA was similar to that of CYP3A7 mRNA in the fetal liver, and CYP3A4 mRNA levels in the fetal liver were about 0.1 times lower than in the adult liver. CYP2E1 showed the highest level of mRNA expression in the liver. The mRNA expression of 30 CYP isoforms (CYP1A1, 1A2, 1B1, 2A6, 2A7, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 2J2, 3A4, 3A5, 3A7, 4A11, 4F2, 4F3, 5A1, 7B1, 8A1, 8B1, 17, 26A1, 27, 27B1, 39A1, 46, and 51) in the liver was successfully detected by this method. CYP2F1, 4B1, 4F8, 11s (11A, 11B1, and 11B2), 19, and 24 mRNA levels were the highest in the lung, lung, prostate, adrenal gland, placenta, and kidney, respectively; however, the mRNA expression of these eight CYP isoforms in the liver was not detected by this method. The mRNA levels of the CYP isoforms deter mined in various human tissues were in good agreement with previously reported data. The method described here has the advantages of high specicity and excellent quantication over a wide range of mRNA concentrations, making it suitable for the evaluation of a large number of samples in the assessment of the expression prole of drugmetabolizing enzymes.

show abstract

Section: Resultssupporting

confidence: 90%

Tissue Distribution of mRNA Expression of Human Cytochrome P450 Isoforms Assessedby High-Sensitivity Real-Time Reverse Transcription PCR

et al. 2003

View full text Add to dashboard Cite

show abstract

“…CYP3A4 is the major cytochrome P450 in adult liver and constitutes 30-40% of the total liver CYP content (Shimada et al 1994). CYP3A7 is the major form in human embryonic, foetal and newborn liver (Kitada et al 1985;Kitada & Kamataki 1994;Lacroix et al 1997;de Wildt et al 1999b). In the period from late foetal to early neonatal life, there appears to be a peak in CYP3A7 activity, then a transition in expression and catalytic activity from predominant CYP3A7 to CYP3A4 such that the total hepatic CYP3A content appears to be relatively stable (Lacroix et al 1997;de Wildt et al 1999b).…”

Section: Cytochrome P450 In the Neonatal Human Livermentioning

confidence: 99%

“…CYP3A7 is the major form in human embryonic, foetal and newborn liver (Kitada et al 1985;Kitada & Kamataki 1994;Lacroix et al 1997;de Wildt et al 1999b). In the period from late foetal to early neonatal life, there appears to be a peak in CYP3A7 activity, then a transition in expression and catalytic activity from predominant CYP3A7 to CYP3A4 such that the total hepatic CYP3A content appears to be relatively stable (Lacroix et al 1997;de Wildt et al 1999b). CYP3A4 expression and activity then reaches 30 to 50% of adult levels from 3 to 12 months of age (Vauzelle-Kervroedan et al 1996;Lacroix et al 1997;de Wildt et al 1999b).…”

Section: Cytochrome P450 In the Neonatal Human Livermentioning

confidence: 99%

“…In the period from late foetal to early neonatal life, there appears to be a peak in CYP3A7 activity, then a transition in expression and catalytic activity from predominant CYP3A7 to CYP3A4 such that the total hepatic CYP3A content appears to be relatively stable (Lacroix et al 1997;de Wildt et al 1999b). CYP3A4 expression and activity then reaches 30 to 50% of adult levels from 3 to 12 months of age (Vauzelle-Kervroedan et al 1996;Lacroix et al 1997;de Wildt et al 1999b). The ontogeny of CYP3A4 and 3A7 activities have been well summarised in the review of de Wildt et al (1999b).…”

Section: Cytochrome P450 In the Neonatal Human Livermentioning

confidence: 99%

“…CYP3A4 expression and activity then reaches 30 to 50% of adult levels from 3 to 12 months of age (Vauzelle-Kervroedan et al 1996;Lacroix et al 1997;de Wildt et al 1999b). The ontogeny of CYP3A4 and 3A7 activities have been well summarised in the review of de Wildt et al (1999b).…”

Section: Cytochrome P450 In the Neonatal Human Livermentioning

confidence: 99%

See 2 more Smart Citations

Neonatal Hepatic Drug Elimination

Gow

Ghabrial

Smallwood

et al. 2001

Pharmacology & Toxicology

104

View full text Add to dashboard Cite

After the transition from in utero to newborn life, the neonate becomes solely reliant upon its own drug clearance processes to metabolise xenobiotics. Whilst most studies of neonatal hepatic drug elimination have focussed upon in vitro expression and activities of drug-metabolising enzymes, the rapid physiological changes in the early neonatal period of life also need to be considered. There are dramatic changes in neonatal liver blood flow and hepatic oxygenation due to the loss of the umbilical blood supply, the increasing portal vein blood flow, and the gradual closure of the ductus venosus shunt during the first week of life. These changes which may well affect the capacity of neonatal hepatic drug metabolism. The hepatic expression of cytochromes P450 1A2, 2C, 2D6, 2E1 and 3A4 develop at different rates in the postnatal period, whilst 3A7 expression diminishes. Hepatic glucuronidation in the human neonate is relatively immature at birth, which contrasts with the considerably more mature neonatal hepatic sulfation activity. Limited in vivo studies show that the human neonate can significantly metabolise xenobiotics but clearance is considerably less compared with the older infant and adult. The neonatal population included in pharmacological studies is highly heterogeneous with respect to age, body weight, ductus venosus closure and disease processes, making it difficult to interpret data arising from human neonatal studies. Studies in the perfused foetal and neonatal sheep liver have demonstrated how the oxidative and conjugative hepatic elimination of drugs by the intact organ is significantly increased during the first week of life, highlighting that future studies will need to consider the profound physiological changes that may influence neonatal hepatic drug elimination shortly after birth.The development of clinical pharmacology has resulted in a more rational approach to drug therapy, as well as a deeper understanding of the factors capable of influencing drug disposition, and hence drug effects. Of these factors, age is of great importance. However, substantial differences in drug disposition not only exist between neonates and adults, but also among premature neonates, term neonates, infants and children.During the last two decades drug disposition in the neonatal period has been studied extensively. A major impetus for these studies seems to have been a series of incidents involving illness or death following the administration of drugs at ratios of dose/body weight innocuous in an adult (Craft et al. 1974;Gershanik et al. 1982). These studies have shown that the transition from neonate to childhood is characterised by the ontogeny of all of the processes of drug absorption, distribution, hepatic metabolism and renal excretion, with the development of hepatic drug metabolism being particularly important.The extent to which the neonatal drug-metabolising en-

show abstract

Pharmacogenetics in Drug Metabolism: Role of Phase I Enzymes

Dolžan

2012

Pharmacogenetics and Individualized Therapy

View full text Add to dashboard Cite

Cytochrome P450 3A

Cited by 496 publications

References 131 publications

Tissue Distribution of mRNA Expression of Human Cytochrome P450 Isoforms Assessedby High-Sensitivity Real-Time Reverse Transcription PCR

Tissue Distribution of mRNA Expression of Human Cytochrome P450 Isoforms Assessedby High-Sensitivity Real-Time Reverse Transcription PCR

Neonatal Hepatic Drug Elimination

Pharmacogenetics in Drug Metabolism: Role of Phase I Enzymes

Contact Info

Product

Resources

About