pbpk model for mmae-based adcs  (Simcyp)

Journal: Pharmaceutics

Article Title: A Physiologically-Based Pharmacokinetic Simulation to Evaluate Approaches to Mitigate Efavirenz-Induced Decrease in Levonorgestrel Exposure with a Contraceptive Implant

doi: 10.3390/pharmaceutics16081050

Figure Lengend Snippet: Values of levonorgestrel physicochemical and PK properties used in the PBPK model.

Article Snippet: Methods: Using a physiologically-based pharmacokinetic (PBPK) model for levonorgestrel that we developed within the Simcyp ® program, we evaluated a higher dose of levonorgestrel implant, a lower dose of efavirenz, and the combination of both, as possible methods to mitigate the interaction.

Techniques:

Journal: Pharmaceutics

Article Title: A Physiologically-Based Pharmacokinetic Simulation to Evaluate Approaches to Mitigate Efavirenz-Induced Decrease in Levonorgestrel Exposure with a Contraceptive Implant

doi: 10.3390/pharmaceutics16081050

Figure Lengend Snippet: Population ( left plot ) and study-specific ( right plot ) predicted levonorgestrel plasma concentration, based on a MEM, versus observed mean concentration from one two-oral dose study without efavirenz (□) and with efavirenz (■) , two single-oral dose studies without efavirenz (+ and ×) [ , ], one single-IV dose study without efavirenz (∆) , and one implant study without efavirenz (○) and with efavirenz (●) . ‘Population’ predictions ( left plot ) use point estimates of parameters for the model, whereas ‘Study-specific’ predictions ( right plot ) consider inter-study variability (i.e., use post hoc parameters). The inset plots enlarge the lower left quadrant for ease of viewing.

Article Snippet: Methods: Using a physiologically-based pharmacokinetic (PBPK) model for levonorgestrel that we developed within the Simcyp ® program, we evaluated a higher dose of levonorgestrel implant, a lower dose of efavirenz, and the combination of both, as possible methods to mitigate the interaction.

Techniques: Clinical Proteomics, Concentration Assay

Journal: Pharmaceutics

Article Title: A Physiologically-Based Pharmacokinetic Simulation to Evaluate Approaches to Mitigate Efavirenz-Induced Decrease in Levonorgestrel Exposure with a Contraceptive Implant

doi: 10.3390/pharmaceutics16081050

Figure Lengend Snippet: Simulated median plasma concentrations 1 month to 5 years after levonorgestrel (LNG) implant placement administered alone or with daily oral efavirenz (EFV) and superimposed mean published data for 150 mg LNG alone or with 600 mg EFV [ , ].

Article Snippet: Methods: Using a physiologically-based pharmacokinetic (PBPK) model for levonorgestrel that we developed within the Simcyp ® program, we evaluated a higher dose of levonorgestrel implant, a lower dose of efavirenz, and the combination of both, as possible methods to mitigate the interaction.

Techniques: Clinical Proteomics

Journal: Pharmaceutics

Article Title: A Physiologically-Based Pharmacokinetic Simulation to Evaluate Approaches to Mitigate Efavirenz-Induced Decrease in Levonorgestrel Exposure with a Contraceptive Implant

doi: 10.3390/pharmaceutics16081050

Figure Lengend Snippet: Simulated median total ( left ) and unbound ( right ) one-year levonorgestrel (LNG) plasma concentration as a function of percent unbound to plasma proteins ( x -axis), implant dose (150 mg or 300 mg) and presence of efavirenz (EFV) 600 mg. Reference concentrations are those associated with the typical percent unbound (1.3%) for LNG 150 mg in the absence of EFV.

Article Snippet: Methods: Using a physiologically-based pharmacokinetic (PBPK) model for levonorgestrel that we developed within the Simcyp ® program, we evaluated a higher dose of levonorgestrel implant, a lower dose of efavirenz, and the combination of both, as possible methods to mitigate the interaction.

Techniques: Clinical Proteomics, Concentration Assay

Journal: Pharmaceutics

Article Title: A Physiologically-Based Pharmacokinetic Simulation to Evaluate Approaches to Mitigate Efavirenz-Induced Decrease in Levonorgestrel Exposure with a Contraceptive Implant

doi: 10.3390/pharmaceutics16081050

Figure Lengend Snippet: Simulated median total (left-axis) and unbound (right-axis) levonorgestrel (LNG) plasma concentration at one-year post-implant placement as a function of LNG dose and efavirenz (EFV) exposure. ‘Fold increase’ refers to varying magnitudes of EFV exposure (average plasma concentrations) associated with 600 mg for putative differing genetic subgroups relative to the general (Reference) population.

Article Snippet: Methods: Using a physiologically-based pharmacokinetic (PBPK) model for levonorgestrel that we developed within the Simcyp ® program, we evaluated a higher dose of levonorgestrel implant, a lower dose of efavirenz, and the combination of both, as possible methods to mitigate the interaction.

Techniques: Clinical Proteomics, Concentration Assay