Metabolism of Omeprazole by Gut Flora in Rats

Watanabe, Kazuhide; Yamashita, S.; Furuno, Katsushi; Kawasaki, Hiromu; Gomita, Yutaka

doi:10.1002/jps.2600840425

Cited by 42 publications

(29 citation statements)

References 8 publications

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“…Moreover, the terminal half-life, V ss , and Cl values were also dose-independent [37]. In the present control rats, the AUC 0-2 h values of omeprazole after intravenous administration at a dose of 20 mg/kg were approximately 2-times that of AUC 0-2 h obtained after intravenous administration at a dose of 10 mg/kg in rats [37]. Hence, the intravenous dose of omeprazole, 20 mg/kg, was arbitrarily chosen in the present study.…”

Section: Discussionmentioning

confidence: 94%

“…After intravenous administration of omeprazole at doses of 2.5, 5 and 10 mg/kg in rats, the AUC 0-2 h (the plasma concentrations of omeprazole were measured up to 1.25, 2.0 and 2.0 h for 2.5, 5 and 10 mg/kg, respectively) values were dose-proportional [37]. Moreover, the terminal half-life, V ss , and Cl values were also dose-independent [37].…”

Section: Discussionmentioning

confidence: 99%

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Effects of enzyme inducers and inhibitors on the pharmacokinetics of intravenous omeprazole in rats

Lee

Shin

Bae

et al. 2006

Biopharm & Drug Disp

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A series of experiments using various inducers and inhibitors of the hepatic microsomal cytochrome P450 (CYP) isozymes were conducted to find CYP isozymes responsible for the metabolism of omeprazole in male Sprague-Dawley rats. Omeprazole, 20 mg/kg, was administered intravenously. In rats pretreated with SKF 525-A (a nonspecific CYP isozyme inhibitor in rats), the time-averaged nonrenal clearance (Cl(nr)) was significantly slower (77.1% decrease) than that in untreated rats. This indicated that omeprazole is metabolized via CYP isozymes in rats. Hence, rats were pretreated with various enzyme inducers and inhibitors. In rats pretreated with 3-methylcholanthrene and dexamethasone (main inducers of CYP1A1/2 and 3A1/2 in rats, respectively), the Cl(nr) values were significantly faster (43.8% and 26.3% increase, respectively). In rats pretreated with troleandomycin and quinine (main inhibitors of CYP3A1/2 and 2D1 in rats, respectively), the Cl(nr) values were significantly slower (20.9% and 12.9% decrease, respectively). However, the Cl(nr) values were not significantly different in rats pretreated with orphenadrine, isoniazid and sulfaphenazole (main inducers of CYP2B1/2 and 2E1, and a main inhibitor of 2C11, respectively, in rats) compared with those of respective control rats. The above data suggested that omeprazole could be mainly metabolized via CYP1A1/2, 3A1/2 and 2D1 in male rats.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Effects of enzyme inducers and inhibitors on the pharmacokinetics of intravenous omeprazole in rats

Lee

Shin

Bae

et al. 2006

Biopharm & Drug Disp

View full text Add to dashboard Cite

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“…orally administered omeprazole is well absorbed and does not reach the distal gut. Thus bacterial enzymes are unlikely to be involved in this metabolism 69 .…”

Section: Sulfoxide Reductionmentioning

confidence: 99%

Human gut microbiota plays a role in the metabolism of drugs

Jourová¹,

Anzenbacher²,

Anzenbacherová³

2016

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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a Background and Aims. The gut microbiome, an aggregate genome of trillions of microorganisms residing in the human gastrointestinal tract, is now known to play a critical role in human health and predisposition to disease. It is also involved in the biotransformation of xenobiotics and several recent studies have shown that the gut microbiota can affect the pharmacokinetics of orally taken drugs with implications for their oral bioavailability. Methods. Review of Pubmed, Web of Science and Science Direct databases for the years 1957-2016. Results and Conclusions. Recent studies make it clear that the human gut microbiota can play a major role in the metabolism of xenobiotics and, the stability and oral bioavailability of drugs. Over the past 50 years, more than 30 drugs have been identified as a substrate for intestinal bacteria. Questions concerning the impact of the gut microbiota on drug metabolism, remain unanswered or only partially answered, namely (i) what are the molecular mechanisms and which bacterial species are involved? (ii) What is the impact of host genotype and environmental factors on the composition and function of the gut microbiota, (iii) To what extent is the composition of the intestinal microbiome stable, transmissible, and resilient to perturbation? (iv) Has past exposure to a given drug any impact on future microbial response, and, if so, for how long? Answering such questions should be an integral part of pharmaceutical research and personalised health care.

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“…This method has the advantage of capturing a greater diversity of organisms and has been successfully applied to identify numerous drugs that are susceptible to microbial metabolism (Valerino et al, 1972;Caldwell and Hawksworth, 1973;Smith and Griffiths, 1974;Powis et al, 1979;Koch and Goldman, 1979;Koch et al, 1980;Lindenbaum et al, 1981;Elmer and Remmel, 1984;Harris et al, 1986;Strong et al, 1987;Shu et al, 1991;DH Kim et al, 1992;Lavrijsen et al, 1995;Watanabe et al, 1995;Kitamura et al, 1997;Sasaki et al, 1997;Basit and Lacey, 2001;Basit et al, 2002;Deng et al, 2011;Li et al, 2012;McCabe et al, 2015). However, when testing a community of microorganisms collectively, inter-strain antagonism may mask This article has not been copyedited and formatted.…”

Section: Mastering Microbial Metabolismmentioning

confidence: 99%

How to Determine the Role of the Microbiome in Drug Disposition

et al. 2018

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With a paradigm shift occurring in health care towards personalized and precision medicine, understanding the numerous environmental factors that impact drug disposition is of paramount importance. The highly diverse and variant nature of the human microbiome is now recognized as a factor driving inter-individual variation in therapeutic outcomes. The purpose of this review is to provide a practical guide on methodology that can be applied to study the effects of microbes on the absorption, distribution, metabolism, and excretion of drugs. We also highlight recent examples of how these methods have been successfully applied to help build the basis for researching the intersection of microbiome and pharmacology. While in vitro and in vivo preclinical models are highlighted, these methods are also relevant in late-phase drug development or even as a part of routine after-market surveillance. These approaches will aid in filling major knowledge gaps for both current and upcoming therapeutics with the long-term goal of achieving a new type of knowledge-based medicine that integrates data on the host and the microbiome.

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Metabolism of Omeprazole by Gut Flora in Rats

Cited by 42 publications

References 8 publications

Effects of enzyme inducers and inhibitors on the pharmacokinetics of intravenous omeprazole in rats

Effects of enzyme inducers and inhibitors on the pharmacokinetics of intravenous omeprazole in rats

Human gut microbiota plays a role in the metabolism of drugs

How to Determine the Role of the Microbiome in Drug Disposition

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