Journal: Pharmaceutics

Article Title: Forecasting Fetal Buprenorphine Exposure through Maternal–Fetal Physiologically Based Pharmacokinetic Modeling

doi: 10.3390/pharmaceutics16030375

Figure Lengend Snippet: Maternal–fetal physiologically based pharmacokinetic (PBPK) model-based predicted and observed maternal buprenorphine plasma concentrations during the ( a ) second trimester, ( b ) third trimester, and ( c ) postpartum period. Pregnant subjects received 8 mg buprenorphine twice daily as sublingual tablets. Blue solid line and shaded area represent the mean concentration–time profile and 5th to 95th percentile range of the virtual population (n = 100), respectively. Open blue circles represent concentration–time data reported by Zhang et al. [ , ].

Article Snippet: To allow the conceptualization of fetal buprenorphine exposure, a maternal–fetal physiologically based pharmacokinetic (PBPK) model for sublingual buprenorphine was developed using Simcyp (v21.0).

Techniques: Clinical Proteomics, Concentration Assay

Journal: Pharmaceutics

Article Title: Forecasting Fetal Buprenorphine Exposure through Maternal–Fetal Physiologically Based Pharmacokinetic Modeling

doi: 10.3390/pharmaceutics16030375

Figure Lengend Snippet: Individual maternal–fetal physiologically based pharmacokinetic (PBPK) model-based predicted and observed maternal and fetal buprenorphine plasma concentrations at delivery. Pregnant women received between 1 and 28 mg buprenorphine daily as sublingual tablets, and individual doses are shown in the lower left corner of each figure subsection. Closed red circles represent observed buprenorphine concentrations in maternal and umbilical cord blood reported by ( a – j ) Bartu et al. and ( k – u ) Wiegand et al. for a total of 21 mother–fetus dyads. Simulated concentration–time profiles with 5th to 95th population percentile ranges (n = 100 mother–fetus dyads) were created either under the presumption that the proportion of the administered dose sublingually absorbed by the expectant mother equals 0.754 × (38.1 − 19.7 × log (Dose)), which is the default absorption extent in the maternal–fetal PBPK model for sublingual tablets (shown in blue and green for maternal and fetal concentrations, respectively), or with the degree of maternal sublingual absorption optimized (across a range of 0.1–99.9%) post hoc to capture the reported maternal concentration–time point as accurately as possible (shown in grayscale). The final degrees of sublingual absorption are shown in the upper right corner of each figure subsection (written in blue and gray to reflect the model’s default and optimized value, respectively).

Article Snippet: To allow the conceptualization of fetal buprenorphine exposure, a maternal–fetal physiologically based pharmacokinetic (PBPK) model for sublingual buprenorphine was developed using Simcyp (v21.0).

Techniques: Clinical Proteomics, Concentration Assay

Journal: Pharmaceutics

Article Title: Forecasting Fetal Buprenorphine Exposure through Maternal–Fetal Physiologically Based Pharmacokinetic Modeling

doi: 10.3390/pharmaceutics16030375

Figure Lengend Snippet: Mean maternal–fetal physiologically based pharmacokinetic (PBPK) model-based predicted maternal (aged 18–45 years) and umbilical cord blood concentrations of buprenorphine early in the second trimester, at the end of the second trimester, and at the end of the third trimester (15, 27, and 40 weeks’ gestational age, respectively) following a standard 16 mg buprenorphine dose as sublingual tablet. The concentration–time curves are juxtaposed with the expected profile of a nonpregnant woman under the same conditions (created using the previously developed base model) .

Article Snippet: To allow the conceptualization of fetal buprenorphine exposure, a maternal–fetal physiologically based pharmacokinetic (PBPK) model for sublingual buprenorphine was developed using Simcyp (v21.0).

Techniques: Concentration Assay

Journal: Pharmaceutics

Article Title: Forecasting Fetal Buprenorphine Exposure through Maternal–Fetal Physiologically Based Pharmacokinetic Modeling

doi: 10.3390/pharmaceutics16030375

Figure Lengend Snippet: Goodness-of-fit plots for the maternal–fetal physiologically based pharmacokinetic (PBPK) model for buprenorphine, showing ( a , b ) predicted vs. observed maternal and ( c , d ) fetal concentrations following administration of buprenorphine sublingual tablets. Coefficients of determination ( R 2 ) and associated p values are shown in the lower right corner of each figure subset. Concentrations were predicted either ( a , c ) under the presumption that the proportion of the administered dose sublingually absorbed by the expectant mother equals 0.754 × (38.1 − 19.7 × log (Dose)), which is the default absorption extent in the maternal–fetal PBPK model for sublingual tablets, or ( b , d ) with the degree of maternal sublingual absorption optimized (across a range of 0.1–99.9%) post hoc to capture the reported maternal concentration–time point as accurately as possible. Blue circles (●) and green diamonds (◆) represent maternal and fetal concentration–time data reported by Bartu et al. and Wiegand et al. , respectively. Dotted lines represent the 2-fold prediction error range. Curved dashed lines represent locally estimated scatterplot smoothing (LOESS) curves.

Article Snippet: To allow the conceptualization of fetal buprenorphine exposure, a maternal–fetal physiologically based pharmacokinetic (PBPK) model for sublingual buprenorphine was developed using Simcyp (v21.0).

Techniques: Concentration Assay

Journal: Pharmaceutics

Article Title: Forecasting Fetal Buprenorphine Exposure through Maternal–Fetal Physiologically Based Pharmacokinetic Modeling

doi: 10.3390/pharmaceutics16030375

Figure Lengend Snippet: Goodness-of-fit plots for the maternal–fetal physiologically based pharmacokinetic (PBPK) model for buprenorphine, showing ( a , b ) dose vs. the ratio between maternal predicted and observed concentrations (concentration fold-difference) and ( c , d ) dose vs. fetal concentration fold-differences. Concentrations were predicted either ( a , c ) under the presumption that the proportion of the administered dose sublingually absorbed by the expectant mother equals 0.754 × (38.1 − 19.7 × log (Dose)), which is the default absorption extent in the maternal–fetal PBPK model for sublingual tablets, or ( b , d ) with the degree of maternal sublingual absorption optimized (across a range of 0.1–99.9%) post hoc to capture the reported maternal concentration–time point as accurately as possible. Blue circles (●) and green diamonds (◆) represent concentration fold-differences obtained from maternal and fetal concentration–time data reported by Bartu et al. and Wiegand et al. , respectively. Dotted lines represent the 2-fold prediction error range. Curved dashed lines represent locally estimated scatterplot smoothing (LOESS) curves.

Article Snippet: To allow the conceptualization of fetal buprenorphine exposure, a maternal–fetal physiologically based pharmacokinetic (PBPK) model for sublingual buprenorphine was developed using Simcyp (v21.0).

Techniques: Concentration Assay

Journal: Drug Metabolism and Disposition

Article Title: Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A Systematic Review of Published Models, Applications, and Model Verification

doi: 10.1124/dmd.115.065920

Figure Lengend Snippet: List of compounds for which Full PBPK models were used to address pharmacological and toxicological questions

Article Snippet: Lu G, Abduljalil K, Jamei M, Johnson TN, Soltani H, Rostami-Hodjegan A. (2012) Physiologically-based pharmacokinetic (PBPK) models for assessing the kinetics of xenobiotics during pregnancy: achievements and shortcomings.

Techniques: Selection, Drug discovery, Concentration Assay, Binding Assay, Clinical Proteomics