SEEING THROUGH THE MIST: ABUNDANCE VERSUS PERCENTAGE. COMMENTARY ON METABOLITES IN SAFETY TESTING

No abstract is available for this paper.

• Publication year

  2005

• Venue

  Drug Metabolism And Disposition

• Publication date

  2005-10-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1124/dmd.105.005041PMID 15985503
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Advances in molecular toxicology-towards understanding idiosyncratic drug toxicity.

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• Drug safety discontinuations in the United Kingdom, the United States, and Spain from 1974 through 1993: A regulatory perspective

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• Clinical and experimental studies linking oxidative metabolism to phenytoin-induced teratogenesis.

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• Bopindolol. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy.

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• Dose‐dependent pharmacokinetics of acetaminophen: Evidence of glutathione depletion in humans

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• Drug discontinuations in the United Kingdom and the United States, 1964 to 1983: Issues of safety

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  1981cited by this paper
• Drug receptors.

  1979cited by this paper
• Metabolism of nomifensine in man and animal species.

  1978cited by this paper
• Phenytoin teratogenesis: correlation between embryopathic effect and covalent binding of putative arene oxide metabolite in gestational tissue.

  1977cited by this paper
• Conformational analysis—CI

  1974cited by this paper

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