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Substrate-dependent modulation of CYP3A4 catalytic activity: analysis of 27 test compounds with four fluorometric substrates.
BFC and DBF appear more suitable as an initial screen for CYP3A4 inhibition, whereas the rank order of sensitivity among the fluorometric substrates varied among the individual inhibitors, on average, BFC dealkylation was the most sensitive to inhibition, while BQ dealkYLation was least sensitive. Expand
Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible.
Azamulin represents an important new chemical tool for use in characterizing the contribution of CYP3A to the metabolism of xenobiotics and is tested toward 18 cytochromes P450. Expand
In Vitro Metabolism and Identification of Human Enzymes Involved in the Metabolism of Methylnaltrexone
The carbonyl reduction of MNTX to M4 and M5 in hepatic cytosol was consistent with previous in vivo observations, although multiple enzymes in the AKR1C subfamily may be involved. Expand
Chemical toxicology: reactive intermediates and their role in pharmacology and toxicology
  • J. Erve
  • Chemistry, Medicine
  • Expert opinion on drug metabolism & toxicology
  • 24 November 2006
This review provides a balanced perspective, primarily focusing on the proposed role of reactive intermediates in drug toxicity, while also highlighting examples in which they are involved in causing the desired pharmacology. Expand
Bioactivation of sitaxentan in liver microsomes, hepatocytes, and expressed human P450s with characterization of the glutathione conjugate by liquid chromatography tandem mass spectrometry.
Overall, the results demonstrated that sitaxentan is capable of facile formation of a reactive ortho-quinone metabolite capable of reacting with glutathione and may rationalize the idiosyncratic nature of the hepatotoxicity that led to its withdrawal. Expand
Metabolism of Intravenous Methylnaltrexone in Mice, Rats, Dogs, and Humans
Methylnaltrexone (MNTX), a selective μ-opioid receptor antagonist, functions as a peripherally acting receptor antagonist in tissues of the gastrointestinal tract and was not extensively metabolized in humans. Expand
Spectral accuracy of molecular ions in an LTQ/Orbitrap mass spectrometer and implications for elemental composition determination
Ten natural products ranging in molecular weight from 639 to 1663 Da were measured on an LTQ/Orbitrap mass spectrometer and several compounds with prominent doubly charged ions allowed comparison of spectral accuracies of singly-versus doubly-charged ions. Expand
Metabolism of Prazosin in Rat, Dog, and Human Liver Microsomes and Cryopreserved Rat and Human Hepatocytes and Characterization of Metabolites by Liquid Chromatography/Tandem Mass Spectrometry
In vitro investigations have revealed additional metabolic transformations of prazosin and have shown the potential of pazosin to undergo bioactivation through metabolism of the furan ring to a reactive intermediate. Expand
Benzoxaborole Antimalarial Agents. Part 5. Lead Optimization of Novel Amide Pyrazinyloxy Benzoxaboroles and Identification of a Preclinical Candidate.
The rapid parasite in vitro reduction and in vivo parasite clearance profile of 46 were similar to those of artemisinin and chloroquine, two rapid-acting antimalarials. Expand
Covalent modification of hemoglobin by carbon disulfide: III. A potential biomarker of effect.
Findings support hemoglobin as a potential preneurotoxic biomarker of effect for CS2 possessing several practical advantages relative to the use of CS2-mediated spectrin cross-linking. Expand