Journal: CPT: Pharmacometrics & Systems Pharmacology

Article Title: Delineating gene–environment effects using virtual twins of patients treated with clozapine

doi: 10.1002/psp4.12886

Figure Lengend Snippet: Patient characteristics in the clinical study.

Article Snippet: Simcyp provides CYP2D6, CYP2C19, and CYP2C9 enzyme abundance data for the following phenotypes (CYP2D6 and CYP2C19 – poor metabolizer [PM], normal metabolizer [NM also known as EM], and ultrarapid metabolizer [UM]; CYP2C9 – PM and NM).

Techniques:

Journal: Drug Metabolism and Disposition

Article Title: Physiologically Based Pharmacokinetic Model of the CYP2D6 Probe Atomoxetine: Extrapolation to Special Populations and Drug-Drug Interactions

doi: 10.1124/dmd.117.076455

Figure Lengend Snippet: The workflow of developing and validating the atomoxetine full-PBPK model and extrapolating the validated model to predict atomoxetine disposition in different ethnicities, special populations, and DDIs.

Article Snippet: The predicted volume of distribution at steady state (Vss) value was 0.74 l/kg, compared with the observed atomoxetine Vss value of 1.02–1.09 l/kg ( Center for Drug Evaluation and Research, 2002 ) following intravenous dosing in healthy subjects. table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Parameter Value Reference Physicochemical Molecular Weight (g/mol) 255.36 Stattera NDA Log P 3.9 NDA p K a 9.8 NDA f u 0.025 NDA B/P 0.623 Simcyp prediction toolbox Absorption F a 0.96 k a (l/h) 1.2 Optimized Q gut (l/h) 11.9 Simcyp prediction toolbox Distribution V ss (l/kg) 0.74 Simcyp prediction full PBPK method 2 Metabolism/elimination CL i.v. (l/h) 16.3 NDA CL r (l/h) 0.185 Sauer et al. (2003) f m,CYP2D6 0.876 Recombinant CL int ( μ l/min/pmol) CYP2D6 25.4 CYP2C19 1.84 P450 enzyme abundance (pmol/mg microsomal protein) CYP2D6 EM 8 (61) a Simcyp default value CYP2C19 EM 14 (40) a Optimized Interaction CYP2D6 K i ( μ M) 34.3 Sauer et al. (2004) CYP3A4 K i ( μ M) 3.6 Sauer et al. (2004) Open in a separate window B/P, blood-to-plasma ratio; CL i.v. , clearance after intravenous administration; CL r , renal clearance; F a , fraction absorbed; f m , fraction metabolized; f u , fraction unbound in plasma; k a , absorption rate constant; K i , inhibition constant; Log P, log octanol:water partition coefficient; Q gut , drug absorption flow to intestine; V ss , volume of distribution at steady state. a Mean value (coefficient of variance).

Techniques:

Journal: Drug Metabolism and Disposition

Article Title: Physiologically Based Pharmacokinetic Model of the CYP2D6 Probe Atomoxetine: Extrapolation to Special Populations and Drug-Drug Interactions

doi: 10.1124/dmd.117.076455

Figure Lengend Snippet: Physicochemical and PK parameters of atomoxetine used in the PBPK model development

Article Snippet: The predicted volume of distribution at steady state (Vss) value was 0.74 l/kg, compared with the observed atomoxetine Vss value of 1.02–1.09 l/kg ( Center for Drug Evaluation and Research, 2002 ) following intravenous dosing in healthy subjects. table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Parameter Value Reference Physicochemical Molecular Weight (g/mol) 255.36 Stattera NDA Log P 3.9 NDA p K a 9.8 NDA f u 0.025 NDA B/P 0.623 Simcyp prediction toolbox Absorption F a 0.96 k a (l/h) 1.2 Optimized Q gut (l/h) 11.9 Simcyp prediction toolbox Distribution V ss (l/kg) 0.74 Simcyp prediction full PBPK method 2 Metabolism/elimination CL i.v. (l/h) 16.3 NDA CL r (l/h) 0.185 Sauer et al. (2003) f m,CYP2D6 0.876 Recombinant CL int ( μ l/min/pmol) CYP2D6 25.4 CYP2C19 1.84 P450 enzyme abundance (pmol/mg microsomal protein) CYP2D6 EM 8 (61) a Simcyp default value CYP2C19 EM 14 (40) a Optimized Interaction CYP2D6 K i ( μ M) 34.3 Sauer et al. (2004) CYP3A4 K i ( μ M) 3.6 Sauer et al. (2004) Open in a separate window B/P, blood-to-plasma ratio; CL i.v. , clearance after intravenous administration; CL r , renal clearance; F a , fraction absorbed; f m , fraction metabolized; f u , fraction unbound in plasma; k a , absorption rate constant; K i , inhibition constant; Log P, log octanol:water partition coefficient; Q gut , drug absorption flow to intestine; V ss , volume of distribution at steady state. a Mean value (coefficient of variance).

Techniques: Molecular Weight, Recombinant