(Q36572637)

15 August 2017

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title

Minimising the potential for metabolic activation in drug discovery (English)

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15 August 2017

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Amit S Kalgutkar

1

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15 August 2017

John R Soglia

series ordinal

2

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15 August 2017

language of work or name

English

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publication date

1 June 2005

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Expert Opinion on Drug Metabolism & Toxicology

15 August 2017

published in

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15 August 2017

volume

1

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15 August 2017

issue

1

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15 August 2017

page(s)

91-142

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Timing of new black box warnings and withdrawals for prescription medications

15 August 2017

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Concordance of the toxicity of pharmaceuticals in humans and in animals

21 January 2018

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Clinical perspectives on xenobiotic-induced hepatotoxicity

21 January 2018

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Selective protein covalent binding and target organ toxicity

21 January 2018

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Metabolism of drugs by leukocytes

21 January 2018

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The danger model: a renewed sense of self

21 January 2018

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New concepts in immunology relevant to idiosyncratic drug reactions: the "danger hypothesis" and innate immune system

21 January 2018

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Cellular mechanisms of T cell mediated drug hypersensitivity.

21 January 2018

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Mechanisms of hepatotoxicity

21 January 2018

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Applications of cytotoxicity assays and pre-lethal mechanistic assays for assessment of human hepatotoxicity potential

21 January 2018

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Protein targets of xenobiotic reactive intermediates

21 January 2018

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The role of metabolic activation in drug-induced hepatotoxicity

21 January 2018

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2,6-diarylaminotetrahydropyrans from reactions of glutaraldehyde with anilines: models for biomolecule cross-linking

21 January 2018

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Identification of adducts formed by reaction of guanine nucleosides with malondialdehyde and structurally related aldehydes

21 January 2018

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The metabolism of alicyclic amines to reactive iminium ion intermediates

21 January 2018

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The development of a higher throughput reactive intermediate screening assay incorporating micro-bore liquid chromatography-micro-electrospray ionization-tandem mass spectrometry and glutathione ethyl ester as an in vitro conjugating agent

21 January 2018

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A high-capacity LC/MS system for the bioanalysis of samples generated from plate-based metabolic screening

21 January 2018

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Drug-protein adducts: an industry perspective on minimizing the potential for drug bioactivation in drug discovery and development

21 January 2018

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Drug-mediated inactivation of cytochrome P450.

21 January 2018

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https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Cross-sensitization to haptens: formation of common haptenic metabolites, T cell recognition of cryptic peptides, and true T cell cross-reactivity

21 January 2018

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On the diversity of oxidative bioactivation reactions on nitrogen-containing xenobiotics

21 January 2018

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https://api.crossref.org/works/10.1517%2F17425255.1.1.91

The metabolic activation of nitroheterocyclic therapeutic agents

21 January 2018

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https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Bioactivation of benzylamine to reactive intermediates in rodents: formation of glutathione, glutamate, and peptide conjugates

21 January 2018

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Interactions of nitrogen-containing xenobiotics with monoamine oxidase (MAO) isozymes A and B: SAR studies on MAO substrates and inhibitors

21 January 2018

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https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Inactivation of monoamine oxidase B by 1-phenylcyclopropylamine: mass spectral evidence for the flavin adduct

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Free radical-mediated oxidative DNA damage in the mechanism of thalidomide teratogenicity

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Drug protein conjugates--VI. Role of glutathione in the metabolism of captopril and captopril plasma protein conjugates

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Quinoids, quinoid radicals, and phenoxyl radicals formed from estrogens and antiestrogens

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Mechanisms of inhibitory and regulatory effects of methylenedioxyphenyl compounds on cytochrome P450-dependent drug oxidation

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Thioether adducts of a new imine reactive intermediate of the pneumotoxin 3-methylindole.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Biotransformation reactions of five-membered aromatic heterocyclic rings

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Mechanism-based inactivation of human recombinant P450 2C9 by the nonsteroidal anti-inflammatory drug suprofen

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Studies on the metabolism of troglitazone to reactive intermediates in vitro and in vivo. Evidence for novel biotransformation pathways involving quinone methide formation and thiazolidinedione ring scission.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Cytochrome P450-catalyzed oxidation of halobenzene derivatives

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Trends in structure-toxicity relationships for carbonyl-containing alpha,beta-unsaturated compounds

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Acyl glucuronide reactivity in perspective: biological consequences

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Updated clinical risk factor analysis of suspected hypersensitivity reactions to abacavir

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Paracetamol toxicity: epidemiology, prevention and costs to the health-care system.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Adverse reactions to alclofenac

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Comparative pharmacokinetic profile of two imidazopyridine drugs: zolpidem and alpidem

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Oxidation of aminopyrine by hypochlorite to a reactive dication: possible implications for aminopyrine-induced agranulocytosis

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Amiodarone liver toxicity about two cases and review of literature

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Is there a link between the phototoxic or antioxidant properties of amiodarone, an antiarrhythmic drug, and its lipophilic character?

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Antimalarial Drug Toxicity

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Genetic predisposition to drug hepatotoxicity: role in hepatitis caused by amineptine, a tricyclic antidepressant

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Clinical pharmacokinetics and pharmacodynamics of bromfenac

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Adverse effects of angiotensin converting enzyme (ACE) inhibitors. An update

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Captopril: pharmacology, metabolism and disposition

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Adverse reactions to new anticonvulsant drugs

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

The fall and rise of chloramphenicol

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Cyclophosphamide toxicity. Characterising and avoiding the problem

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Acrolein mercapturates: synthesis, characterization, and assessment of their role in the bladder toxicity of cyclophosphamide

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

3-Hydroxypropylmercapturic acid: a biologic marker of exposure to allylic and related compounds

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

The metabolism of diclofenac--enzymology and toxicology perspectives

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Risks of agranulocytosis and aplastic anemia in relation to the use of cardiovascular drugs: The International Agranulocytosis and Aplastic Anemia Study.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Interaction of human serum albumin with furosemide glucuronide: a role of albumin in isomerization, hydrolysis, reversible binding and irreversible binding of a 1-O-acyl glucuronide metabolite

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Identification of potentially neurotoxic pyridinium metabolite in the urine of schizophrenic patients treated with haloperidol

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Human anti-endoplasmic reticulum antibodies in sera of patients with halothane-induced hepatitis are directed against a trifluoroacetylated carboxylesterase

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Irreversible protein binding of [14C]imipramine with rat and human liver microsomes

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Nonsteroidal anti-inflammatory drug-induced hepatic disorders. Incidence and prevention

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Iproniazid hepatitis: report of five cases and review of pertinent literature

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Evidence for the involvement of N-methylthiourea, a ring cleavage metabolite, in the hepatotoxicity of methimazole in glutathione-depleted mice: structure-toxicity and metabolic studies

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Drug-associated agranulocytosis: 20 years of reporting in The Netherlands (1974-1994).

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Minocycline-induced lupus. A systematic review

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Mechanism for the anti-thyroid action of minocycline.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Bioactivation of the nontricyclic antidepressant nefazodone to a reactive quinone-imine species in human liver microsomes and recombinant cytochrome P450 3A4.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Pharmacological and biochemical studies with three metabolites of nomifensine

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Free radical intermediates of phenytoin and related teratogens. Prostaglandin H synthase-catalyzed bioactivation, electron paramagnetic resonance spectrometry, and photochemical product analysis.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Bioactivation of phenytoin by human cytochrome P450: characterization of the mechanism and targets of covalent adduct formation.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Practolol metabolism in various small animal species

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Poisoning due to class IA antiarrhythmic drugs. Quinidine, procainamide and disopyramide

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Characterization of glutathione conjugates of the remoxipride hydroquinone metabolite NCQ-344 formed in vitro and detection following oxidation by human neutrophils

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Oxicams: metabolic disposition in man and animals

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Sulfonamide hypersensitivity

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Hepatocellular carcinoma after long-term tamoxifen therapy

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Bioactivation of tamoxifen by recombinant human cytochrome p450 enzymes

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Terbinafine-associated hepatotoxicity

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Identification of a reactive metabolite of terbinafine: insights into terbinafine-induced hepatotoxicity

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Thalidomide teratogenesis: evidence for a toxic arene oxide metabolite

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Ticlopidine as a selective mechanism-based inhibitor of human cytochrome P450 2C19.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Immune mechanisms in tienilic acid associated hepatotoxicity

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Neonatal thrombocytopeniaand congenital malformations associated with administration of tolbutamide to the mother

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

In vitro metabolism of tolcapone to reactive intermediates: relevance to tolcapone liver toxicity

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Monoamine oxidase inhibitors.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

trans-2-phenylcyclopropylamine is a substrate for and inactivator of horseradish peroxidase.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Mechanisms of troglitazone hepatotoxicity

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Valproic acid hepatic fatalities. III. U.S. experience since 1986.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

In vitro metabolism of 2-acetylbenzothiophene: relevance to zileuton hepatotoxicity

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Zimeldine versus amitriptyline in endogenous depression. A double-blind study with special reference to effects on liver function

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Mechanism-based inactivation of CYP3A by HIV protease inhibitors

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Hepatotoxicity associated with ritonavir

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Design, synthesis, and evaluation of metabolism-based analogues of haloperidol incapable of forming MPP+-like species

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Metabolism-dependent neutrophil cytotoxicity of amodiaquine: A comparison with pyronaridine and related antimalarial drugs.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Fluorine substitution can block CYP3A4 metabolism-dependent inhibition: identification of (S)-N-[1-(4-fluoro-3- morpholin-4-ylphenyl)ethyl]-3- (4-fluorophenyl)acrylamide as an orally bioavailable KCNQ2 opener devoid of CYP3A4 metabolism-dependent in

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Structure and stereochemistry of the active metabolite of clopidogrel

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Pharmacology of meloxicam, a new non-steroidal anti-inflammatory drug with an improved safety profile through preferential inhibition of COX-2.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Metabolism and excretion of tolcapone, a novel inhibitor of catechol-O-methyltransferase

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Ranitidine bioavailability and kinetics in normal male subjects

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Disposition of CP-671, 305, a selective phosphodiesterase 4 inhibitor in preclinical species.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Metabolism, pharmacokinetics, and excretion of a highly selective N-methyl-D-aspartate receptor antagonist, traxoprodil, in human cytochrome P450 2D6 extensive and poor metabolizers

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Clinical pharmacokinetics of the prodrug oseltamivir and its active metabolite Ro 64-0802.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Discovery of CP-199,330 and CP-199,331: two potent and orally efficacious cysteinyl LT1 receptor antagonists devoid of liver toxicity

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Evidence for covalent binding of acyl glucuronides to serum albumin via an imine mechanism as revealed by tandem mass spectrometry

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Predictability of the covalent binding of acidic drugs in man.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

A novel approach for predicting acyl glucuronide reactivity via Schiff base formation: development of rapidly formed peptide adducts for LC/MS/MS measurements

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Development of an in vitro screening model for the biosynthesis of acyl glucuronide metabolites and the assessment of their reactivity toward human serum albumin

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Cytochrome P450 3A4-mediated bioactivation of raloxifene: irreversible enzyme inhibition and thiol adduct formation

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Characterization of raloxifene glucuronidation in vitro: contribution of intestinal metabolism to presystemic clearance

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Apparent mechanism-based inhibition of human CYP2D6 in vitro by paroxetine: comparison with fluoxetine and quinidine

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Hepatotoxicity associated with the new antidepressants

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Effects of itraconazole on the plasma kinetics of quazepam and its two active metabolites after a single oral dose of the drug

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Clinical pharmacokinetics of prazosin

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Mechanism-based inactivation of cytochrome P450 3A4 by 17 alpha-ethynylestradiol: evidence for heme destruction and covalent binding to protein

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Animal models of idiosyncratic drug reactions.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

D-penicillamine-induced autoimmunity in the Brown Norway rat: role for both T and non-T splenocytes in adoptive transfer of tolerance

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Tolerance induced by low dose D-penicillamine in the brown Norway rat model of drug-induced autoimmunity is immune-mediated

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Modulation of D-penicillamine-induced autoimmunity in the Brown Norway rat using pharmacological agents that interfere with arachidonic acid metabolism or synthesis of inducible nitric oxide synthase

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Protective role of Kupffer cells in acetaminophen-induced hepatic injury in mice

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Augmentation of aflatoxin B1 hepatotoxicity by endotoxin: involvement of endothelium and the coagulation system

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Underlying endotoxemia augments toxic responses to chlorpromazine: is there a relationship to drug idiosyncrasy?

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Ranitidine treatment during a modest inflammatory response precipitates idiosyncrasy-like liver injury in rats

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Involvement of cyclooxygenase-2 in the potentiation of allyl alcohol-induced liver injury by bacterial lipopolysaccharide

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Bacterial lipopolysaccharide enhances aflatoxin B1 hepatotoxicity in rats by a mechanism that depends on tumor necrosis factor alpha

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

Metabolism of Lamotrigine to a Reactive Arene Oxide Intermediate

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

The pharmacokinetics of captopril and captopril disulfide conjugates in uraemic patients on maintenance dialysis: Comparison with patients with normal renal function

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17425255.1.1.91

21 January 2018

Identifiers

DOI

10.1517/17425255.1.1.91

1 reference

15 August 2017

1 reference