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In vitro drug interactions of cytochrome p450: an evaluation of fluorogenic to conventional substrates.
TLDR
The correlation between IC50 values obtained with fluorogenic and conventional drug probes for structurally diverse inhibitors of the five major human p450 isoforms is examined, showing the care needed when selecting fluorogenic probes and the caution needed when results are used to drive structure-activity relationships with respect to drug interactions.
Epoxidation of olefins by cytochrome P450: evidence from site-specific mutagenesis for hydroperoxo-iron as an electrophilic oxidant.
TLDR
Results and a comparison of the ratios of the rates of epoxidation and hydroxylation support the concept that two different species with electrophilic properties, hydroperoxo-iron (FeO2H)3+ and oxenoid-iron(FeO)3+, can effect olefinEpoxidation.
The Pharmacokinetics, Metabolism, and Clearance Mechanisms of Tofacitinib, a Janus Kinase Inhibitor, in Humans
TLDR
The pharmacokinetic characterization of tofacitinib has been consistent with its clinical experience in drug-drug interaction studies, and Cytochrome P450 (P450) profiling indicated that tofacItinib was mainly metabolized by CYP3A4, with a smaller contribution from CYP2C19.
In vitro metabolism studies on the isoxazole ring scission in the anti-inflammatory agent lefluonomide to its active alpha-cyanoenol metabolite A771726: mechanistic similarities with the cytochrome
TLDR
Results indicate that the C3-H in leflunomide is essential for ring opening, and a mechanism for the p450-mediated ring scission is proposed in which the isoxazole ring nitrogen or oxygen coordinates to the reduced form of the heme followed by charge transfer from p450Fe(II) to the C=N bond or deprotonation of the C4-H, which results in a cleavage of the N-O bond.
Ibuprofen Metabolism in the Liver and Gill of Rainbow Trout, Oncorhynchus mykiss
TLDR
Assays involving the induction and inhibition of specific CYP isozymes support CYP1A2 as a possible metabolic pathway in fish.
BIOACTIVATION OF THE NONTRICYCLIC ANTIDEPRESSANT NEFAZODONE TO A REACTIVE QUINONE-IMINE SPECIES IN HUMAN LIVER MICROSOMES AND RECOMBINANT CYTOCHROME P450 3A4
TLDR
Findings are consistent with the proposal that two-electron oxidation of p-hydroxybuspirone to the corresponding quinone-imine is less favorable due to differences in the protonation state at physiological pH and due to weaker resonance stabilization of the oxidation products as predicted from ab initio measurements.
Pharmacokinetics, Metabolism, and Excretion of Torcetrapib, a Cholesteryl Ester Transfer Protein Inhibitor, in Humans
TLDR
In vitro studies using human subcellular fractions suggested that the initial metabolism of torcetrapib proceeds via CYP3A-mediated decarbamoylation, and subsequent oxidations lead to the major circulating and excretory metabolites M1 and M4.
Role of isozymes of rabbit microsomal cytochrome P-450 in the metabolism of retinoic acid, retinol, and retinal.
TLDR
The results show that the individual forms of P-450 metabolize retinoic acid, retinol, and retinal to multiple products, and they indicate that the amounts formed may be dependent on the exposure of animals to various inducers ofP-450.
Old Yellow enzyme: aromatization of cyclic enones and the mechanism of a novel dismutation reaction.
TLDR
Structural-function relationships in the NADPH-dependent reduction of alpha,beta-unsaturated aldehydes or ketones indicate that increasing alkyl substitution at the beta-carbon results in marked decrease in the rate of reduction of the olefinic bond, consistent with a steric hindrance to hydride transfer at thebeta-carbon.
Pharmacokinetics, Metabolism, and Excretion of the Antidiabetic Agent Ertugliflozin (PF-04971729) in Healthy Male Subjects
TLDR
The data suggest that ertugliflozin is well absorbed in humans, and eliminated largely via glucuronidation, suggestive of moderate metabolic elimination in humans.
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