Drug biotransformation in the placenta

Juchau, Mont R.

doi:10.1016/0163-7258(80)90074-1

Cited by 126 publications

(41 citation statements)

References 84 publications

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“…In addition, the placenta can perform biotransformation and detoxication reactions. In fact, the placenta is capable of carrying out most of the biotransformation reactions that occur in liver (Juchau, 1980). Xenobiotic transporters are present and functional in placenta and may be a missing link between maternal exposure and embryo/ fetal toxicity.…”

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confidence: 99%

The Presence of Xenobiotic Transporters in Rat Placenta

Leazer

Klaassen²

2003

Drug Metab Dispos

114

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ABSTRACT:Understanding the role of transporters in placental handling of xenobiotics across the maternal-fetal interface is essential to evaluate the pharmacological and toxicological potential of therapeutic agents, drugs of abuse, and other xenobiotics to which the mother is exposed during pregnancy. Therefore, the purpose of this study was to assess mRNA levels of various transporters in placenta and to compare these to levels in maternal liver and kidney, predominant organs of excretion, to determine which transporters are likely to have a role in xenobiotic transfer within the placenta. During late stage pregnancy, relative amounts of mRNA levels of 40 genes representing 11 families/group of transporters were assessed in placenta with respect to relative maternal liver and kidney mRNA levels. Members of the following transporter families were assessed: three multidrug resistance (

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confidence: 99%

The Presence of Xenobiotic Transporters in Rat Placenta

Leazer

Klaassen²

2003

Drug Metab Dispos

114

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“…The formation of the glucuronide conjugates of BUP and norBUP was also reported (Cone et al, 1984). During pregnancy, the human placenta plays an important role in the metabolism of endogenous compounds, xenobiotics, and environmental pollutants (Juchau 1980;Contractor, 1983;Nandakumaran et al, 1983, Blanck et al, 1983Roe et al, 1990;Pienimaki et al, 1997). The expression and activity of various P450 isoforms depends on placental gestation age and tissue maturity but is lower than that in the liver (Hakkola et al, 1996a,b).…”

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confidence: 99%

Aromatase Is the Major Enzyme Metabolizing Buprenorphine in Human Placenta

Deshmukh

Nanovskaya²,

Ahmed³

2003

J Pharmacol Exp Ther

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Buprenorphine (BUP) is a partial opiate agonist used for treatment of the adult and the pregnant addicted to this class of narcotics. The kinetic parameters for transplacental transfer and the metabolism of BUP during its perfusion in a placental lobule were the subject of an earlier report from our laboratory. The aim of this investigation is to identify and characterize the enzyme catalyzing the metabolism of BUP in term human placenta. Norbuprenorphine (norBUP) is the only metabolite formed as determined by high performance liquid chromatography and mass spectrometry. The activity of the enzyme responsible for BUP metabolism is highest in the microsomal fraction and lowest in the cytosolic, with the mitochondrial in between. Compounds with selective affinity to the enzyme aromatase (CYP 19), namely 4-hydroxyandrostenedione and aminoglutethimide, caused Ͼ70% inhibition of norBUP formation. Monoclonal antibodies raised against CYP 19 were the most potent inhibitors of BUP dealkylation. A comparison between the data obtained from the saturation isotherm for BUP dealkylation by placental microsomes and a commercially available system of cDNA-expressed CYP 19 indicated similar kinetic parameters, with apparent K m values of 12 Ϯ 4.0 and 14 Ϯ 8.0 M, respectively. Therefore, aromatase is the major enzyme catalyzing the biotransformation of BUP to norBUP in term human placentas obtained from healthy pregnancies. The minor involvement of other cytochrome P450 isoforms or enzyme(s) in the metabolism of BUP in placental tissue cannot be ruled out.

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“…A variety of placental enzymes exist and can be induced by maternal exposure to cigarette smoke and other types of drugs and toxicants (Juchau 1980). Metabolism by the fetus itself can in some cases outweigh the importance of maternal metabolism in terms of fetal toxicant exposure.…”

Section: Analysis Of Toxicokinetic Datamentioning

confidence: 99%

A framework for assessing risks to children from exposure to environmental agents.

Daston

Faustman

Ginsberg

et al. 2004

Environ Health Perspect

100

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In recent years there has been an increasing focus in environmental risk assessment on children as a potentially susceptible population. There also has been growing recognition of the need for a systematic approach for organizing, evaluating, and incorporating the available data on children's susceptibilities in risk assessments. In this article we present a conceptual framework for assessing risks to children from environmental exposures. The proposed framework builds on the problem formulation → analysis → risk characterization paradigm, identifying at each phase the questions and issues of particular importance for characterizing risks to the developing organism (from conception through organ maturation). The framework is presented and discussed from the complementary perspectives of toxicokinetics and toxicodynamics.

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Drug biotransformation in the placenta

Cited by 126 publications

References 84 publications

The Presence of Xenobiotic Transporters in Rat Placenta

The Presence of Xenobiotic Transporters in Rat Placenta

Aromatase Is the Major Enzyme Metabolizing Buprenorphine in Human Placenta

A framework for assessing risks to children from exposure to environmental agents.

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