Differential foetal development of the O‐ and N‐demethylation of codeine and dextromethorphan in man.

Ladona, Margarita G.; Lindström, Björn; Thyr, Charlotte; Peng, Dun-Ren; Rane, Anders

doi:10.1111/j.1365-2125.1991.tb03902.x

Cited by 72 publications

(38 citation statements)

References 29 publications

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“…Ladona et al (1991) were unable to detect CYP2D6 protein by imniunoblotting with anti-human CYP2D6 antibody or dextromethorphan 0-demethylation activity (catalyzed by CYP2D6) in foetal liver samples. In agreement with this, Shimada et ul.…”

Section: Ontogencsis Of Individual P450 Enzymesmentioning

confidence: 93%

Developmental Expression of Cytochrome P450 Enzymes in Human Liver

Hakkola

Tanaka

Pelkonen

1998

Pharmacology & Toxicology

107

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Absrruct: Drug-metabolizing cytochrome P450 enzymes, the major phase I enzymes, are active in human liver already at very early stages of intrauterine development, although presumably at f d y low concentrations and in low numben. During maturation. these enzymes go through various developmental programmes towards adulthood. The major increase both in abundance as well as in number of different enzymes takes place after birth, probably during the first year of life. Detailed information concerning these developmental changes is still limited. The major drug-metabolizing P450 enzymes appear to be primarily members of the CYP3A subfamily in all stages of development. The balance between different members of this subfamily, however, undergoes significant switches from the foetal predominant CYP3A7 to the major adult forni CYP3A4. The ontogcny of the other cytochronie P450 enzymes is less well characterized, but the major switchon appears to occur mainly after birth. Developmental expression of P450 enzymes is one of the key factors determining the pharmacokinetic status of developing individuals both pre-and postnatally.

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Section: Ontogencsis Of Individual P450 Enzymesmentioning

confidence: 93%

Developmental Expression of Cytochrome P450 Enzymes in Human Liver

Hakkola

Tanaka

Pelkonen

1998

Pharmacology & Toxicology

107

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“…This finding was reinforced by our study showing that the N-demethylation of codeine could be induced by carbamazepine ) since hepatic CYP3A4 has been shown to be inducible by medications such as rifampin (Pichard et al 1990;Watkins et al 1989). The CYP3A enzymes play an important role in the metabolism of a growing list of drugs such as cyclosporine A (Kronback et al 1988;Combalbert et al 1989), calcium channel blockers (Guengerich et al 1986a), macrolide antibiotics (Watkins et al 1985), midazolam, triazolam (Kronback et al 1989), quinidine (Kitada et al 1987;Guengerich et al 1986b), lignocaine (Bargetzi et al 1989) and dextromethorphan (Gorski et al 1994;JacqzAigrain et al 1993;Ladona et al 1991). Although large interindividual variation in the CYP3A activity has been found, a polymorphic characteristic has not been proven (Schellens et al 1988).…”

Section: Introductionmentioning

confidence: 98%

Different effects of inhibitors on the O - and N -demethylation of codeine in human liver microsomes

Qy¹,

Säwe²

1997

European Journal of Clinical Pharmacology

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“…Based on the inability to detect the O-demethylation of dextromethorphan, early studies by Ladona et al (1991) suggested the absence of CYP2D6 expression in fetal liver. With three 11-to 13-week fetal liver samples, Shimada et al (1996b) also failed to detect CYP2D6 immunoreactive protein.…”

Section: Ontogeny Of the Cytochromes P450mentioning

confidence: 99%

The Ontogeny of Human Drug-Metabolizing Enzymes: Phase I Oxidative Enzymes: Table 1

Hines

McCarver²

2002

J Pharmacol Exp Ther

320

180

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Although some patterns are beginning to emerge, our knowledge of human phase I drug-metabolizing enzyme developmental expression remains far from complete. Expression has been observed as early as organogenesis, but this appears restricted to a few enzymes. At least two of the enzyme families that are expressed in the fetal liver exhibit a temporal switch in the immediate perinatal period (e.g., CYP3A7 to CYP3A4/3A5 and FMO1 to FMO3), whereas others show a progressive change in isoform expression through gestation (e.g., the class I alcohol dehydrogenases). Many of the phase I drug-metabolizing enzyme exhibit dynamic perinatal expression changes that are regulated primarily by mechanisms linked to birth and secondarily to maturity. A few of these enzymes are not detectable until well after birth, suggesting that birth is necessary but not sufficient for the onset of expression (e.g., CYP1A2). Tissue-specific expression adds to the complexity during ontogeny. For example, CYP3A7 expression is restricted to the fetal liver. However, with few exceptions, complete temporal relationship information during development is not known. Furthermore, most studies have concentrated on hepatic expression and much less is known about extrahepatic developmental events.

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Differential foetal development of the O‐ and N‐demethylation of codeine and dextromethorphan in man.

Cited by 72 publications

References 29 publications

Developmental Expression of Cytochrome P450 Enzymes in Human Liver

Developmental Expression of Cytochrome P450 Enzymes in Human Liver

Different effects of inhibitors on the O - and N -demethylation of codeine in human liver microsomes

The Ontogeny of Human Drug-Metabolizing Enzymes: Phase I Oxidative Enzymes: Table 1

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