Journal: Archives of Toxicology

Article Title: Quantitative in vitro-to-in vivo extrapolation of human adrenergic and trace amine-associated receptor 1 potencies of pre-workout supplement ingredients using physiologically based kinetic modelling-based reverse dosimetry

doi: 10.1007/s00204-025-03992-7

Figure Lengend Snippet: Compound depletion of a starting concentration of 1 µM of (A) β-methylphenethylamine, (B) dimethylphenethylamine, (C) halostachine, (D) higenamine, (E) hordenine, (F) isopropyloctopamine, (G) methylsynephrine, (H) methyltyramine, (I) p-octopamine, (J) p-synephrine, (K) phenethylamine and (L) tyramine in incubations with human liver S9 (HSL9) and co-factor mix (= full reaction mix; dots ), in incubations with co-factor mix and without HLS9 (= w/o human liver S9; squares ) and in incubations with HLS9 and without co-factor mix (= w/o co-factor mix; triangles ); data points (± SD) are shown as the natural logarithm (Ln) of the percentage of the parent compound at time point zero; K represents the elimination rate constant (/min) derived from the slope of compound depletion in full reaction mix incubations

Article Snippet: In vitro intrinsic hepatic clearance (CL int ) values of the phenethylamine analogues were determined in experiments with pooled human liver S9 (HLS9; Corning, Woburn, MA, USA and Gibco, USA), by measuring the rate of compound depletion.

Techniques: Concentration Assay, Derivative Assay

Journal: Archives of Toxicology

Article Title: Quantitative in vitro-to-in vivo extrapolation of human adrenergic and trace amine-associated receptor 1 potencies of pre-workout supplement ingredients using physiologically based kinetic modelling-based reverse dosimetry

doi: 10.1007/s00204-025-03992-7

Figure Lengend Snippet: Normalised sensitivity coefficients (NSCs) of the C max plasma venous simulations to the critical input parameters for all studied phenethylamine (PEA) analogues at an oral dose of 1 mg/kg bw; (A) β-methylphenethylamine, (B) dimethylphenethylamine, (C) halostachine, (D) higenamine, (E) hordenine, (F) isopropyloctopamine, (G) methylsynephrine, (H) methyltyramine, (I) phenethylamine, (J) p-octopamine, (K) p-synephrine and (L) tyramine. FQre = fractional tissue blood flow rest of body, FQte = fractional testes blood, FQsp = fractional spleen blood flow, FQmu = fractional muscle blood flow, FQh = fractional hepatic blood flow, FQki = fractional kidney blood flow, FQhe = fractional heart blood flow, FQgu = fractional gut blood flow, FQbr = fractional brain blood flow, FQbo = fractional bone blood flow, FQad = fractional adipose tissue blood flow, CO = cardiac output, FVre = fractional volume rest of body, FVpl = fractional volume plasma, FVar = fractional volume arterial blood, FVve = fractional volume venous blood, FVte = fractional volume testes, FVsp = fractional volume spleen, FVsk = fractional volume skin, FVmu = fractional volume muscle, FVlu = fractional volume lung, FVli = fractional volume liver, FVki = fractional volume kidney, FVhe = fractional volume heart, FVgu = fractional volume gut, FVbr = fractional volume brain, FVbo = fractional volume bone, FVad = fractional volume adipose tissue, BW = body weight, BP = blood/plasma ratio, fuliver = fraction unbound liver, fup = fraction unbound in plasma, CLint = intrinsic clearance, fuinc = fraction unbound in human liver S9 incubation, SF = scaling factor of human liver S9 to a whole human liver, Kpre = rest of body:plasma partition coefficient, Kpte = testes:plasma partition coefficient, Kpsp = spleen:plasma partition coefficient, Kpsk = skin:plasma partition coefficient, Kpmu = muscle:plasma partition coefficient, Kplu = lung:plasma partition coefficient, Kpli = liver:plasma partition coefficient, Kpki = kidney:plasma partition coefficient, Kphe = heart:plasma partition coefficient, Kpgu = gut:plasma partition coefficient, Kpbr = brain:plasma partition coefficient, Kpbo = bone:plasma partition coefficient, Kpad = adipose:plasma partition coefficient, fa = fraction absorbed, ka = absorption rate constant

Article Snippet: In vitro intrinsic hepatic clearance (CL int ) values of the phenethylamine analogues were determined in experiments with pooled human liver S9 (HLS9; Corning, Woburn, MA, USA and Gibco, USA), by measuring the rate of compound depletion.

Techniques: Clinical Proteomics, Analogues, Incubation

Journal: Archives of Toxicology

Article Title: Quantitative in vitro-to-in vivo extrapolation of human adrenergic and trace amine-associated receptor 1 potencies of pre-workout supplement ingredients using physiologically based kinetic modelling-based reverse dosimetry

doi: 10.1007/s00204-025-03992-7

Figure Lengend Snippet: Normalised sensitivity coefficients (NSCs) of the C max plasma venous simulations to the most critical input parameters for all studied phenethylamine (PEA) analogues at an oral dose of 1 mg/kg bw; for each parameter, data points of the 12 different PEA analogues are shown; FQmu, fractional muscle blood flow; FQh, fractional hepatic blood flow (venous side); FQki, fractional kidney blood flow; FQbr, fractional brain blood flow; FQre, fractional tissue blood flow rest of body; FVli, fractional liver volume; fuliver, fraction unbound in liver; Clint, in vitro intrinsic hepatic metabolic clearance; fuinc, fraction unbound in the in vitro liver S9 incubation; SF, scaling factor for mg liver S9 per gram liver; fa, fraction absorbed; ka, absorption rate constant

Article Snippet: In vitro intrinsic hepatic clearance (CL int ) values of the phenethylamine analogues were determined in experiments with pooled human liver S9 (HLS9; Corning, Woburn, MA, USA and Gibco, USA), by measuring the rate of compound depletion.

Techniques: Clinical Proteomics, Analogues, In Vitro, Incubation

Journal: Archives of Toxicology

Article Title: Quantitative in vitro-to-in vivo extrapolation of human adrenergic and trace amine-associated receptor 1 potencies of pre-workout supplement ingredients using physiologically based kinetic modelling-based reverse dosimetry

doi: 10.1007/s00204-025-03992-7

Figure Lengend Snippet: Correlations of Normalized Sensitivity Coefficients (NSCs) and the modelled intrinsic hepatic metabolic intrinsic clearance (CL met ) for the NSCs of (A) CLint (= in vitro intrinsic hepatic metabolic clearance), (B) FQh (= fractional hepatic blood flow, venous side), (C) FVli (= fractional liver volume), (D) fuliver (= fraction unbound in liver), (E) fuinc (= fraction unbound in the in vitro liver S9 incubation) and (F) SF (= scaling factor for mg liver S9 per gram liver)

Article Snippet: In vitro intrinsic hepatic clearance (CL int ) values of the phenethylamine analogues were determined in experiments with pooled human liver S9 (HLS9; Corning, Woburn, MA, USA and Gibco, USA), by measuring the rate of compound depletion.

Techniques: In Vitro, Incubation