simcyp© pregnancy population model  (Simcyp)

Journal: Clinical Pharmacokinetics

Article Title: Prediction of Maternal and Fetal Doravirine Exposure by Integrating Physiologically Based Pharmacokinetic Modeling and Human Placenta Perfusion Experiments

doi: 10.1007/s40262-022-01127-0

Figure Lengend Snippet: Parameters of the mechanistic placenta model

Article Snippet: Therefore, the primary study aim was to predict maternal and fetal doravirine exposure by integrating data from human placenta perfusion experiments in a full-body Simcyp pregnancy PBPK model. To do so, we describe a method for parameterization of the permeability-limited placenta model in Simcyp.

Techniques:

Journal: Clinical Pharmacokinetics

Article Title: Prediction of Maternal and Fetal Doravirine Exposure by Integrating Physiologically Based Pharmacokinetic Modeling and Human Placenta Perfusion Experiments

doi: 10.1007/s40262-022-01127-0

Figure Lengend Snippet: Structure of the pregnancy physiologically based pharmacokinetic (PBPK) model in the PBPK platform Simcyp

Article Snippet: Therefore, the primary study aim was to predict maternal and fetal doravirine exposure by integrating data from human placenta perfusion experiments in a full-body Simcyp pregnancy PBPK model. To do so, we describe a method for parameterization of the permeability-limited placenta model in Simcyp.

Techniques:

Journal: Clinical Pharmacokinetics

Article Title: Prediction of Maternal and Fetal Doravirine Exposure by Integrating Physiologically Based Pharmacokinetic Modeling and Human Placenta Perfusion Experiments

doi: 10.1007/s40262-022-01127-0

Figure Lengend Snippet: Predicted mean doravirine total plasma concentration at steady state after treatment with A , B doravirine 100 mg QD or C , D 100 mg BID using the pregnancy physiologically based pharmacokinetic model ( n = 100 subjects). The in vivo target of 0.23 mg/L was derived from in vivo exposure–response analysis . BID twice daily, QD once daily, w weeks

Article Snippet: Therefore, the primary study aim was to predict maternal and fetal doravirine exposure by integrating data from human placenta perfusion experiments in a full-body Simcyp pregnancy PBPK model. To do so, we describe a method for parameterization of the permeability-limited placenta model in Simcyp.

Techniques: Clinical Proteomics, Concentration Assay, In Vivo, Derivative Assay

Journal: Clinical Pharmacokinetics

Article Title: Prediction of Maternal and Fetal Doravirine Exposure by Integrating Physiologically Based Pharmacokinetic Modeling and Human Placenta Perfusion Experiments

doi: 10.1007/s40262-022-01127-0

Figure Lengend Snippet: Sensitivity analysis of the estimated placental parameters using the pregnancy physiologically based pharmacokinetic model ( n = 100 subjects). Sensitivity of CL pdm input on the doravirine A maternal plasma concentration and B fetal venous blood concentration. Sensitivity of CL pdf input on the doravirine, C maternal plasma concentration and D fetal venous blood concentration. The 2.5th and 97.5th percentile of the typical CL pdf and CL pdm are estimated with the mechanistic placenta model. Sensitivity of the FUp impute on the doravirine, E maternal plasma concentration and F fetal venous blood concentration. Sensitivity of the experimental placenta perfusion configuration on the doravirine, G maternal plasma concentration and H fetal venous blood concentration. CL pdf clearance between fetal part of the placenta and the placental barrier, CL pdm clearance between maternal part of the placenta and the placental barrier, FU P fraction unbound in the placental barrier

Article Snippet: Therefore, the primary study aim was to predict maternal and fetal doravirine exposure by integrating data from human placenta perfusion experiments in a full-body Simcyp pregnancy PBPK model. To do so, we describe a method for parameterization of the permeability-limited placenta model in Simcyp.

Techniques: Clinical Proteomics, Concentration Assay

Journal: Clinical Pharmacokinetics

Article Title: Prediction of Maternal and Fetal Doravirine Exposure by Integrating Physiologically Based Pharmacokinetic Modeling and Human Placenta Perfusion Experiments

doi: 10.1007/s40262-022-01127-0

Figure Lengend Snippet:

Article Snippet: Therefore, the primary study aim was to predict maternal and fetal doravirine exposure by integrating data from human placenta perfusion experiments in a full-body Simcyp pregnancy PBPK model. To do so, we describe a method for parameterization of the permeability-limited placenta model in Simcyp.

Techniques: Derivative Assay