Omeprazole is an aryl hydrocarbon-like inducer of human hepatic cytochrome P450

Diaz, Dominique; Fabrev, Isabelle; Daujat, Martine; Aubert, Bernadette; Bories, P; Michel, H; Maurel, Patrick

doi:10.1016/0016-5085(90)90963-2

Cited by 287 publications

(129 citation statements)

References 32 publications

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“…Most a synergistic effect on blood coagulation. Omeprazole has been reported to be an inducer of new drugs are screened for their potential to interact in this way and the problem becomes exacerbated when CYP1A1 and CYP1A2 in human hepatocytes [60 ] and enterocytes [ 61], but whether this effect occurs in vivo the new drug is a suspect teratogen.…”

Section: Mechanism Of Enzyme Inductionmentioning

confidence: 99%

Relevance of induction of human drug‐metabolizing enzymes: pharmacological and toxicological implications

Park

Kitteringham

Pirmohamed

et al. 1996

Brit J Clinical Pharma

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1Human drug‐metabolizing systems can be induced, or activated, by a large number of exogenous agents including drugs, alcohol, components in the diet and cigarette smoke, as well as by endogenous factors. 2Such perturbation of enzyme activity undoubtedly contributes to both intra‐ and inter‐individual variation both with respect to the rate and route of metabolism for a particular drug. Induction may, in theory, either attenuate the pharmacological response or exacerbate the toxicity of a particular drug, or both. 3The clinical impact of enzyme induction will depend upon the number of different enzyme isoforms affected and the magnitude of the inductive response within an individual, and also on the therapeutic indices of the affected substrates. 4The toxicological implications will be determined either by any change in the route of metabolism, or by a disturbance of the balance between activation and detoxication processes, which may be isozyme selective.

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Section: Mechanism Of Enzyme Inductionmentioning

confidence: 99%

Relevance of induction of human drug‐metabolizing enzymes: pharmacological and toxicological implications

Park

Kitteringham

Pirmohamed

et al. 1996

Brit J Clinical Pharma

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“…Cytochrome P-450 isoform-specific enzyme activities, ethoxyresorufin deethylase (IA), aniline hydroxylase (liE) and erythromicin demethylase (IliA), were assayed using previously published techniques [7,10,11]. Microsomes were diluted to 0.2 mg/ml in 0.1 M potassium phosphate, pH 7.4, and incubated at 37°C for 5 min in the presence of the appropriate substrate.…”

Section: Determination Of Monooxygenase Activitiesmentioning

confidence: 99%

Cytokine‐mediated production of nitric oxide in isolated rat hepatocytes is dependent on cytochrome P‐450III activity

Kuo

Abe

1995

FEBS Letters

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To investigate the role of the cytochrome P-450 system in NO synthesis, cytochrome P-450IIIA, IIE and IA activities were specifically inhibited by cimetidine (IIIA), clotrimazole (IIIA), benzoflavone (IA) and disulfiram (IIE) in a model of cultured rat hepatocytes. Cytokine-induced NO synthesis was significantly decreased in the presence of cimetidine and clotrimazole. Kinetic analysis revealed a non-competitive mode of inhibition (K i = 21 mM, cimetidine; K i = 13/xM, clotrimazole). Reverse transcriptase-PCR and immunoblot analysis revealed no significant change in steady state levels of iNOS mRNA and protein expression with P-450IIIA inhibition. Purified iNOS enzyme activity was not altered. These data suggest that cytokinemediated hepatocyte synthesis of NO is dependent upon P-450IIIA activity, which functions in a post-translational capacity.

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“…These two inducers seemed to exert similar effects in vitro and in vivo, however, we noticed wide variations in the induction from one culture to another. This interculture variability in the response to the inducer has already been observed with other inducers and other forms of P450 [39]. It could result from a number of distinct contributions including the quality of the culture, origin of the tissue (effect of the pathology) and genetic factors.…”

Section: Immunological Reactivity Of Anti-(p450 Fa Igg) Against Micromentioning

confidence: 53%

Purification of two cytochrome P450 isozymes related to CYP2A and CYP3A gene families from monkey (baboon, Papio papio) liver microsomes

Dalet-Beluche

Boulenc

Fabre

et al. 1992

European Journal of Biochemistry

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Two cytochrome P450 isozymes, FA and FI, were isolated and characterized from liver microsomes of phenobarbital-induced baboons (Pupio papio). The cytochrome FA possesses the same Nterminal amino acid sequence as P450 MK2 from crab-eating monkeys (Macaca irus) and closely resembles the human P450 3A isozymes. This cytochrome was able to oxidize nifedipine and hydroxylate testosterone at the 68 position. The second baboon cytochrome (FI) is closely related to the P450 2A subfamily and has the same N-terminal sequence as human P450 2A7. Like human P450 2A forms, it is highly active as a coumarin 7-hydroxylase. Antibodies against P450 FA and FI crossreact with two human liver proteins of 51 kDa and 49 kDa, respectively. The concentration of the first protein in the human samples, was five-times greater than the second. However, the latter showed marked interindividual variation. In primary cultures of human hepatocytes, rifampicin is a strong inducer of the 51-kDa protein and a moderate inducer of the 49-kDa protein, while phenobarbital has the opposite effect on the two proteins.

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Omeprazole is an aryl hydrocarbon-like inducer of human hepatic cytochrome P450

Cited by 287 publications

References 32 publications

Relevance of induction of human drug‐metabolizing enzymes: pharmacological and toxicological implications

Relevance of induction of human drug‐metabolizing enzymes: pharmacological and toxicological implications

Cytokine‐mediated production of nitric oxide in isolated rat hepatocytes is dependent on cytochrome P‐450III activity

Purification of two cytochrome P450 isozymes related to CYP2A and CYP3A gene families from monkey (baboon, Papio papio) liver microsomes

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