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parameter values for tolvaptan  (DILIsym Services Inc)

 
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    DILIsym Services Inc parameter values for tolvaptan
    The effect of 24 h treatment of <t>tolvaptan,</t> DM-4103 and DM-4107 on basal mitochondrial respiratory function (fmoles O 2 /min/cell) in HepG2 cells. Cells were treated with control media or compound in a 5-point dose response regimen (tolvaptan at: 0.01, 0.1, 1, 20, and 50 µM or DM-4103 or DM-4107 at: 1, 20, 50, 100 and 200 µM) for 24 h prior to respirometry experiments. Oxygen consumption rate (OCR) results were normalized to cell number. Data are presented as the average ± SEM for 3 independent experiments. Statistical significance is denoted by an asterisk (* P ≤ .05) for one-way ANOVA with Dunnett’s multiple comparison test to compare each concentration to control for a given compound. Two-way ANOVAs with a Bonferonni multiple comparison test was used to compare compounds: # P ≤ .05 (DM-4103 vs DM-4107); @ P ≤ .05 (tolvaptan vs DM-4103); & P ≤ .05 (tolvaptan vs DM-4107).
    Parameter Values For Tolvaptan, supplied by DILIsym Services Inc, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/parameter values for tolvaptan/product/DILIsym Services Inc
    Average 90 stars, based on 1 article reviews
    parameter values for tolvaptan - by Bioz Stars, 2026-03
    90/100 stars

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    1) Product Images from "Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors"

    Article Title: Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors

    Journal: Toxicological Sciences

    doi: 10.1093/toxsci/kfw193

    The effect of 24 h treatment of tolvaptan, DM-4103 and DM-4107 on basal mitochondrial respiratory function (fmoles O 2 /min/cell) in HepG2 cells. Cells were treated with control media or compound in a 5-point dose response regimen (tolvaptan at: 0.01, 0.1, 1, 20, and 50 µM or DM-4103 or DM-4107 at: 1, 20, 50, 100 and 200 µM) for 24 h prior to respirometry experiments. Oxygen consumption rate (OCR) results were normalized to cell number. Data are presented as the average ± SEM for 3 independent experiments. Statistical significance is denoted by an asterisk (* P ≤ .05) for one-way ANOVA with Dunnett’s multiple comparison test to compare each concentration to control for a given compound. Two-way ANOVAs with a Bonferonni multiple comparison test was used to compare compounds: # P ≤ .05 (DM-4103 vs DM-4107); @ P ≤ .05 (tolvaptan vs DM-4103); & P ≤ .05 (tolvaptan vs DM-4107).
    Figure Legend Snippet: The effect of 24 h treatment of tolvaptan, DM-4103 and DM-4107 on basal mitochondrial respiratory function (fmoles O 2 /min/cell) in HepG2 cells. Cells were treated with control media or compound in a 5-point dose response regimen (tolvaptan at: 0.01, 0.1, 1, 20, and 50 µM or DM-4103 or DM-4107 at: 1, 20, 50, 100 and 200 µM) for 24 h prior to respirometry experiments. Oxygen consumption rate (OCR) results were normalized to cell number. Data are presented as the average ± SEM for 3 independent experiments. Statistical significance is denoted by an asterisk (* P ≤ .05) for one-way ANOVA with Dunnett’s multiple comparison test to compare each concentration to control for a given compound. Two-way ANOVAs with a Bonferonni multiple comparison test was used to compare compounds: # P ≤ .05 (DM-4103 vs DM-4107); @ P ≤ .05 (tolvaptan vs DM-4103); & P ≤ .05 (tolvaptan vs DM-4107).

    Techniques Used: Control, Comparison, Concentration Assay

    Parameters Optimized to Data in the DILIsym PBPK Sub-Model for Tolvaptan.
    Figure Legend Snippet: Parameters Optimized to Data in the DILIsym PBPK Sub-Model for Tolvaptan.

    Techniques Used: Clinical Proteomics

    Parameters Changed between the Renally Sufficient and the Renally Impaired SimPops
    Figure Legend Snippet: Parameters Changed between the Renally Sufficient and the Renally Impaired SimPops

    Techniques Used: Activity Assay

    List of Mechanistic Investigation Simulations and the Mechanisms that Were Turned On and Off for Each Simulation of Tolvaptan Administered 90/30 mg Daily for 180 Days
    Figure Legend Snippet: List of Mechanistic Investigation Simulations and the Mechanisms that Were Turned On and Off for Each Simulation of Tolvaptan Administered 90/30 mg Daily for 180 Days

    Techniques Used:

    List of Parameters Included in the SimPops Used for This Investigation and The Ranges For Each Parameter Relative to Their Average Values
    Figure Legend Snippet: List of Parameters Included in the SimPops Used for This Investigation and The Ranges For Each Parameter Relative to Their Average Values

    Techniques Used:

    Comparison between single dose clinical data for 30 mg, dark red, 60 mg, cyan, and 120 mg, dark green , and range of Renally Sufficient SimPops simulation results for (a) tolvaptan plasma concentrations; (b) DM-4103 plasma concentrations (note: data from the 120 mg study were unavailable for this analyte; see ); (c) DM-4107 plasma concentrations. Dark circles represent the average of the clinical data; stars represent the maximum and minimum value measured in the clinical trial. Simulation results for the 30 mg study are in red, simulation results for the 60 mg study are in blue, and simulation results for the 120 mg study are in green.
    Figure Legend Snippet: Comparison between single dose clinical data for 30 mg, dark red, 60 mg, cyan, and 120 mg, dark green , and range of Renally Sufficient SimPops simulation results for (a) tolvaptan plasma concentrations; (b) DM-4103 plasma concentrations (note: data from the 120 mg study were unavailable for this analyte; see ); (c) DM-4107 plasma concentrations. Dark circles represent the average of the clinical data; stars represent the maximum and minimum value measured in the clinical trial. Simulation results for the 30 mg study are in red, simulation results for the 60 mg study are in blue, and simulation results for the 120 mg study are in green.

    Techniques Used: Comparison, Clinical Proteomics

    Comparison between Renally Sufficient SimPops and day 21 tolvaptan plasma concentrations after 90/30 mg split daily dosing ( Boertien et al. , 2013 ). The clinical data are represented by symbols (black squares) whereas the simulation results for individual simulated patients are represented by solid lines.
    Figure Legend Snippet: Comparison between Renally Sufficient SimPops and day 21 tolvaptan plasma concentrations after 90/30 mg split daily dosing ( Boertien et al. , 2013 ). The clinical data are represented by symbols (black squares) whereas the simulation results for individual simulated patients are represented by solid lines.

    Techniques Used: Comparison, Clinical Proteomics

    Comparison between Renally Impaired SimPops and day 21 tolvaptan plasma concentrations after 90/30 mg split daily dosing ( Boertien et al. , 2013 ). The clinical data are represented by symbols (black squares) whereas the simulation results for individual simulated patients are represented by solid lines.
    Figure Legend Snippet: Comparison between Renally Impaired SimPops and day 21 tolvaptan plasma concentrations after 90/30 mg split daily dosing ( Boertien et al. , 2013 ). The clinical data are represented by symbols (black squares) whereas the simulation results for individual simulated patients are represented by solid lines.

    Techniques Used: Comparison, Clinical Proteomics

    DILIsym Toxicity Parameter Values for Tolvaptan Toxicity Simulations
    Figure Legend Snippet: DILIsym Toxicity Parameter Values for Tolvaptan Toxicity Simulations

    Techniques Used: Inhibition

    Comparison of simulation results and in vitro data for tolvaptan- and DM-4103-induced inhibition of HepG2 oxygen consumption rate. Simulations were conducted in MITOsym and were used to identify parameter values for compound-mediated ETC inhibition that permit simulations to reproduce the in vitro data. The intracellular compound concentration was either assumed to be equivalent to the nominal media concentration or was estimated based on the liver:plasma ratio derived from simulations using the PBPK sub-model. MITOsym parameter values identified with the estimated intracellular compound concentrations were the ones translated to DILIsym and used for toxicity simulations.
    Figure Legend Snippet: Comparison of simulation results and in vitro data for tolvaptan- and DM-4103-induced inhibition of HepG2 oxygen consumption rate. Simulations were conducted in MITOsym and were used to identify parameter values for compound-mediated ETC inhibition that permit simulations to reproduce the in vitro data. The intracellular compound concentration was either assumed to be equivalent to the nominal media concentration or was estimated based on the liver:plasma ratio derived from simulations using the PBPK sub-model. MITOsym parameter values identified with the estimated intracellular compound concentrations were the ones translated to DILIsym and used for toxicity simulations.

    Techniques Used: Comparison, In Vitro, Inhibition, Concentration Assay, Clinical Proteomics, Derivative Assay



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    parameter values for tolvaptan  (DILIsym Services Inc)
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    DILIsym Services Inc parameter values for tolvaptan
    The effect of 24 h treatment of <t>tolvaptan,</t> DM-4103 and DM-4107 on basal mitochondrial respiratory function (fmoles O 2 /min/cell) in HepG2 cells. Cells were treated with control media or compound in a 5-point dose response regimen (tolvaptan at: 0.01, 0.1, 1, 20, and 50 µM or DM-4103 or DM-4107 at: 1, 20, 50, 100 and 200 µM) for 24 h prior to respirometry experiments. Oxygen consumption rate (OCR) results were normalized to cell number. Data are presented as the average ± SEM for 3 independent experiments. Statistical significance is denoted by an asterisk (* P ≤ .05) for one-way ANOVA with Dunnett’s multiple comparison test to compare each concentration to control for a given compound. Two-way ANOVAs with a Bonferonni multiple comparison test was used to compare compounds: # P ≤ .05 (DM-4103 vs DM-4107); @ P ≤ .05 (tolvaptan vs DM-4103); & P ≤ .05 (tolvaptan vs DM-4107).
    Parameter Values For Tolvaptan, supplied by DILIsym Services Inc, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/parameter values for tolvaptan/product/DILIsym Services Inc
    Average 90 stars, based on 1 article reviews
    parameter values for tolvaptan - by Bioz Stars, 2026-03
    90/100 stars
    		  Buy from Supplier

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    The effect of 24 h treatment of tolvaptan, DM-4103 and DM-4107 on basal mitochondrial respiratory function (fmoles O 2 /min/cell) in HepG2 cells. Cells were treated with control media or compound in a 5-point dose response regimen (tolvaptan at: 0.01, 0.1, 1, 20, and 50 µM or DM-4103 or DM-4107 at: 1, 20, 50, 100 and 200 µM) for 24 h prior to respirometry experiments. Oxygen consumption rate (OCR) results were normalized to cell number. Data are presented as the average ± SEM for 3 independent experiments. Statistical significance is denoted by an asterisk (* P ≤ .05) for one-way ANOVA with Dunnett’s multiple comparison test to compare each concentration to control for a given compound. Two-way ANOVAs with a Bonferonni multiple comparison test was used to compare compounds: # P ≤ .05 (DM-4103 vs DM-4107); @ P ≤ .05 (tolvaptan vs DM-4103); & P ≤ .05 (tolvaptan vs DM-4107).

    Journal: Toxicological Sciences

    Article Title: Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors

    doi: 10.1093/toxsci/kfw193

    Figure Lengend Snippet: The effect of 24 h treatment of tolvaptan, DM-4103 and DM-4107 on basal mitochondrial respiratory function (fmoles O 2 /min/cell) in HepG2 cells. Cells were treated with control media or compound in a 5-point dose response regimen (tolvaptan at: 0.01, 0.1, 1, 20, and 50 µM or DM-4103 or DM-4107 at: 1, 20, 50, 100 and 200 µM) for 24 h prior to respirometry experiments. Oxygen consumption rate (OCR) results were normalized to cell number. Data are presented as the average ± SEM for 3 independent experiments. Statistical significance is denoted by an asterisk (* P ≤ .05) for one-way ANOVA with Dunnett’s multiple comparison test to compare each concentration to control for a given compound. Two-way ANOVAs with a Bonferonni multiple comparison test was used to compare compounds: # P ≤ .05 (DM-4103 vs DM-4107); @ P ≤ .05 (tolvaptan vs DM-4103); & P ≤ .05 (tolvaptan vs DM-4107).

    Article Snippet: To increase confidence that the DILIsym parameter values for tolvaptan reasonably captured “safe” tolvaptan scenarios (in addition to the DILI scenarios of interest), the 60 mg daily dose for 60 days tolvaptan dosage regimen was simulated in the Renally Sufficient SimPops.

    Techniques: Control, Comparison, Concentration Assay

    Parameters Optimized to Data in the DILIsym PBPK Sub-Model for Tolvaptan.

    Journal: Toxicological Sciences

    Article Title: Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors

    doi: 10.1093/toxsci/kfw193

    Figure Lengend Snippet: Parameters Optimized to Data in the DILIsym PBPK Sub-Model for Tolvaptan.

    Article Snippet: To increase confidence that the DILIsym parameter values for tolvaptan reasonably captured “safe” tolvaptan scenarios (in addition to the DILI scenarios of interest), the 60 mg daily dose for 60 days tolvaptan dosage regimen was simulated in the Renally Sufficient SimPops.

    Techniques: Clinical Proteomics

    Parameters Changed between the Renally Sufficient and the Renally Impaired SimPops

    Journal: Toxicological Sciences

    Article Title: Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors

    doi: 10.1093/toxsci/kfw193

    Figure Lengend Snippet: Parameters Changed between the Renally Sufficient and the Renally Impaired SimPops

    Article Snippet: To increase confidence that the DILIsym parameter values for tolvaptan reasonably captured “safe” tolvaptan scenarios (in addition to the DILI scenarios of interest), the 60 mg daily dose for 60 days tolvaptan dosage regimen was simulated in the Renally Sufficient SimPops.

    Techniques: Activity Assay

    List of Mechanistic Investigation Simulations and the Mechanisms that Were Turned On and Off for Each Simulation of Tolvaptan Administered 90/30 mg Daily for 180 Days

    Journal: Toxicological Sciences

    Article Title: Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors

    doi: 10.1093/toxsci/kfw193

    Figure Lengend Snippet: List of Mechanistic Investigation Simulations and the Mechanisms that Were Turned On and Off for Each Simulation of Tolvaptan Administered 90/30 mg Daily for 180 Days

    Article Snippet: To increase confidence that the DILIsym parameter values for tolvaptan reasonably captured “safe” tolvaptan scenarios (in addition to the DILI scenarios of interest), the 60 mg daily dose for 60 days tolvaptan dosage regimen was simulated in the Renally Sufficient SimPops.

    Techniques:

    List of Parameters Included in the SimPops Used for This Investigation and The Ranges For Each Parameter Relative to Their Average Values

    Journal: Toxicological Sciences

    Article Title: Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors

    doi: 10.1093/toxsci/kfw193

    Figure Lengend Snippet: List of Parameters Included in the SimPops Used for This Investigation and The Ranges For Each Parameter Relative to Their Average Values

    Article Snippet: To increase confidence that the DILIsym parameter values for tolvaptan reasonably captured “safe” tolvaptan scenarios (in addition to the DILI scenarios of interest), the 60 mg daily dose for 60 days tolvaptan dosage regimen was simulated in the Renally Sufficient SimPops.

    Techniques:

    Comparison between single dose clinical data for 30 mg, dark red, 60 mg, cyan, and 120 mg, dark green , and range of Renally Sufficient SimPops simulation results for (a) tolvaptan plasma concentrations; (b) DM-4103 plasma concentrations (note: data from the 120 mg study were unavailable for this analyte; see ); (c) DM-4107 plasma concentrations. Dark circles represent the average of the clinical data; stars represent the maximum and minimum value measured in the clinical trial. Simulation results for the 30 mg study are in red, simulation results for the 60 mg study are in blue, and simulation results for the 120 mg study are in green.

    Journal: Toxicological Sciences

    Article Title: Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors

    doi: 10.1093/toxsci/kfw193

    Figure Lengend Snippet: Comparison between single dose clinical data for 30 mg, dark red, 60 mg, cyan, and 120 mg, dark green , and range of Renally Sufficient SimPops simulation results for (a) tolvaptan plasma concentrations; (b) DM-4103 plasma concentrations (note: data from the 120 mg study were unavailable for this analyte; see ); (c) DM-4107 plasma concentrations. Dark circles represent the average of the clinical data; stars represent the maximum and minimum value measured in the clinical trial. Simulation results for the 30 mg study are in red, simulation results for the 60 mg study are in blue, and simulation results for the 120 mg study are in green.

    Article Snippet: To increase confidence that the DILIsym parameter values for tolvaptan reasonably captured “safe” tolvaptan scenarios (in addition to the DILI scenarios of interest), the 60 mg daily dose for 60 days tolvaptan dosage regimen was simulated in the Renally Sufficient SimPops.

    Techniques: Comparison, Clinical Proteomics

    Comparison between Renally Sufficient SimPops and day 21 tolvaptan plasma concentrations after 90/30 mg split daily dosing ( Boertien et al. , 2013 ). The clinical data are represented by symbols (black squares) whereas the simulation results for individual simulated patients are represented by solid lines.

    Journal: Toxicological Sciences

    Article Title: Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors

    doi: 10.1093/toxsci/kfw193

    Figure Lengend Snippet: Comparison between Renally Sufficient SimPops and day 21 tolvaptan plasma concentrations after 90/30 mg split daily dosing ( Boertien et al. , 2013 ). The clinical data are represented by symbols (black squares) whereas the simulation results for individual simulated patients are represented by solid lines.

    Article Snippet: To increase confidence that the DILIsym parameter values for tolvaptan reasonably captured “safe” tolvaptan scenarios (in addition to the DILI scenarios of interest), the 60 mg daily dose for 60 days tolvaptan dosage regimen was simulated in the Renally Sufficient SimPops.

    Techniques: Comparison, Clinical Proteomics

    Comparison between Renally Impaired SimPops and day 21 tolvaptan plasma concentrations after 90/30 mg split daily dosing ( Boertien et al. , 2013 ). The clinical data are represented by symbols (black squares) whereas the simulation results for individual simulated patients are represented by solid lines.

    Journal: Toxicological Sciences

    Article Title: Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors

    doi: 10.1093/toxsci/kfw193

    Figure Lengend Snippet: Comparison between Renally Impaired SimPops and day 21 tolvaptan plasma concentrations after 90/30 mg split daily dosing ( Boertien et al. , 2013 ). The clinical data are represented by symbols (black squares) whereas the simulation results for individual simulated patients are represented by solid lines.

    Article Snippet: To increase confidence that the DILIsym parameter values for tolvaptan reasonably captured “safe” tolvaptan scenarios (in addition to the DILI scenarios of interest), the 60 mg daily dose for 60 days tolvaptan dosage regimen was simulated in the Renally Sufficient SimPops.

    Techniques: Comparison, Clinical Proteomics

    DILIsym Toxicity Parameter Values for Tolvaptan Toxicity Simulations

    Journal: Toxicological Sciences

    Article Title: Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors

    doi: 10.1093/toxsci/kfw193

    Figure Lengend Snippet: DILIsym Toxicity Parameter Values for Tolvaptan Toxicity Simulations

    Article Snippet: To increase confidence that the DILIsym parameter values for tolvaptan reasonably captured “safe” tolvaptan scenarios (in addition to the DILI scenarios of interest), the 60 mg daily dose for 60 days tolvaptan dosage regimen was simulated in the Renally Sufficient SimPops.

    Techniques: Inhibition

    Comparison of simulation results and in vitro data for tolvaptan- and DM-4103-induced inhibition of HepG2 oxygen consumption rate. Simulations were conducted in MITOsym and were used to identify parameter values for compound-mediated ETC inhibition that permit simulations to reproduce the in vitro data. The intracellular compound concentration was either assumed to be equivalent to the nominal media concentration or was estimated based on the liver:plasma ratio derived from simulations using the PBPK sub-model. MITOsym parameter values identified with the estimated intracellular compound concentrations were the ones translated to DILIsym and used for toxicity simulations.

    Journal: Toxicological Sciences

    Article Title: Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors

    doi: 10.1093/toxsci/kfw193

    Figure Lengend Snippet: Comparison of simulation results and in vitro data for tolvaptan- and DM-4103-induced inhibition of HepG2 oxygen consumption rate. Simulations were conducted in MITOsym and were used to identify parameter values for compound-mediated ETC inhibition that permit simulations to reproduce the in vitro data. The intracellular compound concentration was either assumed to be equivalent to the nominal media concentration or was estimated based on the liver:plasma ratio derived from simulations using the PBPK sub-model. MITOsym parameter values identified with the estimated intracellular compound concentrations were the ones translated to DILIsym and used for toxicity simulations.

    Article Snippet: To increase confidence that the DILIsym parameter values for tolvaptan reasonably captured “safe” tolvaptan scenarios (in addition to the DILI scenarios of interest), the 60 mg daily dose for 60 days tolvaptan dosage regimen was simulated in the Renally Sufficient SimPops.

    Techniques: Comparison, In Vitro, Inhibition, Concentration Assay, Clinical Proteomics, Derivative Assay