Search results for: Jan L. Wahlstrom

Items from 1 to 6 out of 6 results

article

Meta‐analysis of hepatic cytochrome P450 ontogeny to underwrite the prediction of pediatric pharmacokinetics using physiologically based pharmacokinetic modeling

Vijay V. Upreti, Jan L. Wahlstrom

The Journal of Clinical Pharmacology > 56 > 3 > 266 - 283

The accurate prediction of pharmacokinetics (PK) is fundamental to underwriting safety and efficacy in pediatric clinical trials; age‐dependent PK may be observed with pediatrics because of the growth and maturation processes that occur during development. Understanding the ontogeny of drug‐metabolizing enzymes is a critical enabler for pediatric PK prediction, as enzyme expression or activity may...

article

Differential Time-Dependent Inactivation of P450 3A4 and P450 3A5 by Raloxifene: A Key Role for C239 in Quenching Reactive Intermediates

Josh T. Pearson, Jan L. Wahlstrom, Leslie J. Dickmann, Santosh Kumar, more

Chemical Research in Toxicology > 2007 > 20 > 12 > 1778 - 1786

article

Pharmacokinetic evaluation of a 1,3-dicyclohexylurea nanosuspension formulation to support early efficacy assessment

Jan L. Wahlstrom, Po-Chang Chiang, Sarbani Ghosh, Chad J. Warren, more

Nanoscale Research Letters > 2007 > 2 > 6 > 291-296

Time and resource constraints necessitate increasingly early decisions to advance or halt pre-clinical drug discovery programs. Early discovery or “tool” compounds may be potent inhibitors of new targets, but all too often they exhibit poor pharmaceutical and pharmacokinetic properties that make early assessment of in vivo efficacy difficult. 1,3-Dicyclohexylurea, a potent and selective inhibitor...

article

Activation of cytochrome P450 2C9-mediated metabolism: mechanistic evidence in support of kinetic observations

J. Matthew Hutzler, Larry C. Wienkers, Jan L. Wahlstrom, Timothy J. Carlson, more

Archives of Biochemistry and Biophysics > 2003 > 410 > 1 > 16-24

Studies were designed to investigate the possible mechanisms associated with the kinetic observation of CYP2C9 activation by dapsone and its phase I metabolite, N-hydroxydapsone. Kinetic studies suggested that dapsone activated CYP2C9-mediated flurbiprofen 4 ^' -hydroxylation by decreasing the K _m (α=0.2) and increasing the V _m _a _x (β=1.9). Interestingly, N-hydroxydapsone...

article

Use of Kinetic Isotope Effects to Delineate the Role of Phenylalanine 87 in P450BM-3

Dan A Rock, Anthony E Boitano, Jan L Wahlstrom, Denise A Rock, more

Bioorganic Chemistry > 2002 > 30 > 2 > 107-118

The substrate oxidation rates of P450 _BM-3 are unparalleled in the cytochrome P450 (CYP) superfamily of enzymes. Furthermore, the bacterial enzyme, originating from Bacillus megaterium, has been used repeatedly as a model to study the metabolism of mammalian P450s. A specific example is presented where studying P450 _BM-3 substrate dynamics can define important enzyme-substrate characteristics,...

article

Benign Synthesis of 2-Ethylhexanoic Acid by Cytochrome P450cam: Enzymatic, Crystallographic, and Theoretical Studies ^†

Kevin J. French, Michael D. Strickler, Dan A. Rock, Denise A. Rock, more

Biochemistry > 2001 > 40 > 32 > 9532 - 9538

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Search results for: Jan L. Wahlstrom

Meta‐analysis of hepatic cytochrome P450 ontogeny to underwrite the prediction of pediatric pharmacokinetics using physiologically based pharmacokinetic modeling

Differential Time-Dependent Inactivation of P450 3A4 and P450 3A5 by Raloxifene: A Key Role for C239 in Quenching Reactive Intermediates

Pharmacokinetic evaluation of a 1,3-dicyclohexylurea nanosuspension formulation to support early efficacy assessment

Activation of cytochrome P450 2C9-mediated metabolism: mechanistic evidence in support of kinetic observations

Use of Kinetic Isotope Effects to Delineate the Role of Phenylalanine 87 in P450BM-3

Benign Synthesis of 2-Ethylhexanoic Acid by Cytochrome P450cam: Enzymatic, Crystallographic, and Theoretical Studies †

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Benign Synthesis of 2-Ethylhexanoic Acid by Cytochrome P450cam: Enzymatic, Crystallographic, and Theoretical Studies ^†