Journal: British Journal of Clinical Pharmacology

Article Title: A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration

doi: 10.1111/bcp.13368

Figure Lengend Snippet: Compartmental structure of the full buprenorphine intravenous (IV) and sublingual (SL) physiologically based pharmacokinetic models. The schematic shows how IV and SL administrations were modelled. EHC, enterohepatic circulation

Article Snippet: The accuracies of the predicted means of C max were within 80–125% for all the studies (Table ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 caption a7 Predicted and observed concentration–time profiles following single sublingual (SL) doses of buprenorphine (BUP) in 100 virtual healthy subjects. (A) Plot of the final model built with an 8 mg SL single dose of BUP, in comparison with the observed data from Ciraulo et al . 46 . (B) Intrastudy validation plot with a single dose of 4 mg SL BUP, as observed by Ciraulo et al . 46 . (C and D) Interstudy validation plots with a single dose of 8 mg and 16 mg SL BUP, respectively, as observed by Harris et al . 47 .

Techniques:

Journal: British Journal of Clinical Pharmacology

Article Title: A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration

doi: 10.1111/bcp.13368

Figure Lengend Snippet: Distribution parameters for the buprenorphine profile

Article Snippet: The accuracies of the predicted means of C max were within 80–125% for all the studies (Table ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 caption a7 Predicted and observed concentration–time profiles following single sublingual (SL) doses of buprenorphine (BUP) in 100 virtual healthy subjects. (A) Plot of the final model built with an 8 mg SL single dose of BUP, in comparison with the observed data from Ciraulo et al . 46 . (B) Intrastudy validation plot with a single dose of 4 mg SL BUP, as observed by Ciraulo et al . 46 . (C and D) Interstudy validation plots with a single dose of 8 mg and 16 mg SL BUP, respectively, as observed by Harris et al . 47 .

Techniques:

Journal: British Journal of Clinical Pharmacology

Article Title: A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration

doi: 10.1111/bcp.13368

Figure Lengend Snippet: Intrinsic clearance and intersystem extrapolation factor (ISEF) values associated with enzymes primarily involved in buprenorphine metabolism

Article Snippet: The accuracies of the predicted means of C max were within 80–125% for all the studies (Table ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 caption a7 Predicted and observed concentration–time profiles following single sublingual (SL) doses of buprenorphine (BUP) in 100 virtual healthy subjects. (A) Plot of the final model built with an 8 mg SL single dose of BUP, in comparison with the observed data from Ciraulo et al . 46 . (B) Intrastudy validation plot with a single dose of 4 mg SL BUP, as observed by Ciraulo et al . 46 . (C and D) Interstudy validation plots with a single dose of 8 mg and 16 mg SL BUP, respectively, as observed by Harris et al . 47 .

Techniques:

Journal: British Journal of Clinical Pharmacology

Article Title: A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration

doi: 10.1111/bcp.13368

Figure Lengend Snippet: Intravenous buprenorphine clinical pharmacokinetic studies

Article Snippet: The accuracies of the predicted means of C max were within 80–125% for all the studies (Table ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 caption a7 Predicted and observed concentration–time profiles following single sublingual (SL) doses of buprenorphine (BUP) in 100 virtual healthy subjects. (A) Plot of the final model built with an 8 mg SL single dose of BUP, in comparison with the observed data from Ciraulo et al . 46 . (B) Intrastudy validation plot with a single dose of 4 mg SL BUP, as observed by Ciraulo et al . 46 . (C and D) Interstudy validation plots with a single dose of 8 mg and 16 mg SL BUP, respectively, as observed by Harris et al . 47 .

Techniques:

Journal: British Journal of Clinical Pharmacology

Article Title: A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration

doi: 10.1111/bcp.13368

Figure Lengend Snippet: Sublingual buprenorphine (BUP) clinical pharmacokinetic single‐dose studies considered for modelling

Article Snippet: The accuracies of the predicted means of C max were within 80–125% for all the studies (Table ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 caption a7 Predicted and observed concentration–time profiles following single sublingual (SL) doses of buprenorphine (BUP) in 100 virtual healthy subjects. (A) Plot of the final model built with an 8 mg SL single dose of BUP, in comparison with the observed data from Ciraulo et al . 46 . (B) Intrastudy validation plot with a single dose of 4 mg SL BUP, as observed by Ciraulo et al . 46 . (C and D) Interstudy validation plots with a single dose of 8 mg and 16 mg SL BUP, respectively, as observed by Harris et al . 47 .

Techniques:

Journal: British Journal of Clinical Pharmacology

Article Title: A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration

doi: 10.1111/bcp.13368

Figure Lengend Snippet: Sublingual (SL) buprenorphine dosing allocation between depot and nondepot components

Article Snippet: The accuracies of the predicted means of C max were within 80–125% for all the studies (Table ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 caption a7 Predicted and observed concentration–time profiles following single sublingual (SL) doses of buprenorphine (BUP) in 100 virtual healthy subjects. (A) Plot of the final model built with an 8 mg SL single dose of BUP, in comparison with the observed data from Ciraulo et al . 46 . (B) Intrastudy validation plot with a single dose of 4 mg SL BUP, as observed by Ciraulo et al . 46 . (C and D) Interstudy validation plots with a single dose of 8 mg and 16 mg SL BUP, respectively, as observed by Harris et al . 47 .

Techniques:

Journal: British Journal of Clinical Pharmacology

Article Title: A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration

doi: 10.1111/bcp.13368

Figure Lengend Snippet: Sublingual buprenorphine (BUP) clinical pharmacokinetic multiple‐dose studies considered for modelling

Article Snippet: The accuracies of the predicted means of C max were within 80–125% for all the studies (Table ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 caption a7 Predicted and observed concentration–time profiles following single sublingual (SL) doses of buprenorphine (BUP) in 100 virtual healthy subjects. (A) Plot of the final model built with an 8 mg SL single dose of BUP, in comparison with the observed data from Ciraulo et al . 46 . (B) Intrastudy validation plot with a single dose of 4 mg SL BUP, as observed by Ciraulo et al . 46 . (C and D) Interstudy validation plots with a single dose of 8 mg and 16 mg SL BUP, respectively, as observed by Harris et al . 47 .

Techniques:

Journal: British Journal of Clinical Pharmacology

Article Title: A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration

doi: 10.1111/bcp.13368

Figure Lengend Snippet: Predicted and observed concentration–time profiles following a single intravenous (IV) push doses of buprenorphine (BUP). (A) Plot of the final model built with a single dose of 8 mg IV BUP, in comparison with the observed data from Huestis et al. 43. (B) Interstudy validation plot with a single dose of 0.3 mg IV BUP, as observed by Bai et al. 43. (C, D, E and F) Intrastudy validation plots with single doses of 2, 4, 12 and 16 mg IV BUP, respectively, as observed by Huestis et al. 42 0–24 h pharmacokinetic simulations are shown here

Article Snippet: The accuracies of the predicted means of C max were within 80–125% for all the studies (Table ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 caption a7 Predicted and observed concentration–time profiles following single sublingual (SL) doses of buprenorphine (BUP) in 100 virtual healthy subjects. (A) Plot of the final model built with an 8 mg SL single dose of BUP, in comparison with the observed data from Ciraulo et al . 46 . (B) Intrastudy validation plot with a single dose of 4 mg SL BUP, as observed by Ciraulo et al . 46 . (C and D) Interstudy validation plots with a single dose of 8 mg and 16 mg SL BUP, respectively, as observed by Harris et al . 47 .

Techniques: Concentration Assay, Comparison, Biomarker Discovery

Journal: British Journal of Clinical Pharmacology

Article Title: A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration

doi: 10.1111/bcp.13368

Figure Lengend Snippet: Goodness of fit for intravenous buprenorphine model in healthy subjects

Article Snippet: The accuracies of the predicted means of C max were within 80–125% for all the studies (Table ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 caption a7 Predicted and observed concentration–time profiles following single sublingual (SL) doses of buprenorphine (BUP) in 100 virtual healthy subjects. (A) Plot of the final model built with an 8 mg SL single dose of BUP, in comparison with the observed data from Ciraulo et al . 46 . (B) Intrastudy validation plot with a single dose of 4 mg SL BUP, as observed by Ciraulo et al . 46 . (C and D) Interstudy validation plots with a single dose of 8 mg and 16 mg SL BUP, respectively, as observed by Harris et al . 47 .

Techniques: Biomarker Discovery

Journal: British Journal of Clinical Pharmacology

Article Title: A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration

doi: 10.1111/bcp.13368

Figure Lengend Snippet: Steady‐state predicted and observed concentration–time profiles following daily sublingual (SL) doses of buprenorphine (BUP) in healthy subjects. (A, B, and C) Interstudy validation plots with 16 mg, 24 mg and 32 mg SL BUP, respectively, as observed by Compton et al. 49

Article Snippet: The accuracies of the predicted means of C max were within 80–125% for all the studies (Table ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 caption a7 Predicted and observed concentration–time profiles following single sublingual (SL) doses of buprenorphine (BUP) in 100 virtual healthy subjects. (A) Plot of the final model built with an 8 mg SL single dose of BUP, in comparison with the observed data from Ciraulo et al . 46 . (B) Intrastudy validation plot with a single dose of 4 mg SL BUP, as observed by Ciraulo et al . 46 . (C and D) Interstudy validation plots with a single dose of 8 mg and 16 mg SL BUP, respectively, as observed by Harris et al . 47 .

Techniques: Concentration Assay, Biomarker Discovery

Journal: British Journal of Clinical Pharmacology

Article Title: A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration

doi: 10.1111/bcp.13368

Figure Lengend Snippet: Goodness of fit for sublingual buprenorphine models in healthy volunteers at steady state

Article Snippet: The accuracies of the predicted means of C max were within 80–125% for all the studies (Table ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 caption a7 Predicted and observed concentration–time profiles following single sublingual (SL) doses of buprenorphine (BUP) in 100 virtual healthy subjects. (A) Plot of the final model built with an 8 mg SL single dose of BUP, in comparison with the observed data from Ciraulo et al . 46 . (B) Intrastudy validation plot with a single dose of 4 mg SL BUP, as observed by Ciraulo et al . 46 . (C and D) Interstudy validation plots with a single dose of 8 mg and 16 mg SL BUP, respectively, as observed by Harris et al . 47 .

Techniques: Biomarker Discovery

Journal: British Journal of Clinical Pharmacology

Article Title: A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration

doi: 10.1111/bcp.13368

Figure Lengend Snippet: Predicted and observed concentration–time profiles following single sublingual (SL) doses of buprenorphine (BUP) in 100 virtual healthy subjects. (A) Plot of the final model built with an 8 mg SL single dose of BUP, in comparison with the observed data from Ciraulo et al. 46. (B) Intrastudy validation plot with a single dose of 4 mg SL BUP, as observed by Ciraulo et al. 46. (C and D) Interstudy validation plots with a single dose of 8 mg and 16 mg SL BUP, respectively, as observed by Harris et al. 47. The 0–24 h period in 48 h and 72 h simulations are shown here

Article Snippet: The accuracies of the predicted means of C max were within 80–125% for all the studies (Table ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 caption a7 Predicted and observed concentration–time profiles following single sublingual (SL) doses of buprenorphine (BUP) in 100 virtual healthy subjects. (A) Plot of the final model built with an 8 mg SL single dose of BUP, in comparison with the observed data from Ciraulo et al . 46 . (B) Intrastudy validation plot with a single dose of 4 mg SL BUP, as observed by Ciraulo et al . 46 . (C and D) Interstudy validation plots with a single dose of 8 mg and 16 mg SL BUP, respectively, as observed by Harris et al . 47 .

Techniques: Concentration Assay, Comparison, Biomarker Discovery

Journal: British Journal of Clinical Pharmacology

Article Title: A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration

doi: 10.1111/bcp.13368

Figure Lengend Snippet: Goodness of fit for sublingual buprenorphine model in healthy subjects

Article Snippet: The accuracies of the predicted means of C max were within 80–125% for all the studies (Table ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 caption a7 Predicted and observed concentration–time profiles following single sublingual (SL) doses of buprenorphine (BUP) in 100 virtual healthy subjects. (A) Plot of the final model built with an 8 mg SL single dose of BUP, in comparison with the observed data from Ciraulo et al . 46 . (B) Intrastudy validation plot with a single dose of 4 mg SL BUP, as observed by Ciraulo et al . 46 . (C and D) Interstudy validation plots with a single dose of 8 mg and 16 mg SL BUP, respectively, as observed by Harris et al . 47 .

Techniques: Biomarker Discovery

Journal: British Journal of Clinical Pharmacology

Article Title: A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration

doi: 10.1111/bcp.13368

Figure Lengend Snippet: Predicted plasma and brain concentration–time profiles following a 16 mg sublingual (SL) dose of buprenorphine (BUP) in healthy subjects; mu‐opioid receptor availability is simulated on the secondary axis. Conc., concentration

Article Snippet: The accuracies of the predicted means of C max were within 80–125% for all the studies (Table ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 caption a7 Predicted and observed concentration–time profiles following single sublingual (SL) doses of buprenorphine (BUP) in 100 virtual healthy subjects. (A) Plot of the final model built with an 8 mg SL single dose of BUP, in comparison with the observed data from Ciraulo et al . 46 . (B) Intrastudy validation plot with a single dose of 4 mg SL BUP, as observed by Ciraulo et al . 46 . (C and D) Interstudy validation plots with a single dose of 8 mg and 16 mg SL BUP, respectively, as observed by Harris et al . 47 .

Techniques: Clinical Proteomics, Concentration Assay

Journal: British Journal of Clinical Pharmacology

Article Title: A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration

doi: 10.1111/bcp.13368

Figure Lengend Snippet: Results from mass balance study following administration of radiolabelled intravenous buprenorphine (BUP) 58

Article Snippet: The accuracies of the predicted means of C max were within 80–125% for all the studies (Table ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 caption a7 Predicted and observed concentration–time profiles following single sublingual (SL) doses of buprenorphine (BUP) in 100 virtual healthy subjects. (A) Plot of the final model built with an 8 mg SL single dose of BUP, in comparison with the observed data from Ciraulo et al . 46 . (B) Intrastudy validation plot with a single dose of 4 mg SL BUP, as observed by Ciraulo et al . 46 . (C and D) Interstudy validation plots with a single dose of 8 mg and 16 mg SL BUP, respectively, as observed by Harris et al . 47 .

Techniques:

Journal: British Journal of Clinical Pharmacology

Article Title: A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration

doi: 10.1111/bcp.13368

Figure Lengend Snippet: Summary of buprenorphine physiochemical parameters

Article Snippet: The accuracies of the predicted means of C max were within 80–125% for all the studies (Table ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 caption a7 Predicted and observed concentration–time profiles following single sublingual (SL) doses of buprenorphine (BUP) in 100 virtual healthy subjects. (A) Plot of the final model built with an 8 mg SL single dose of BUP, in comparison with the observed data from Ciraulo et al . 46 . (B) Intrastudy validation plot with a single dose of 4 mg SL BUP, as observed by Ciraulo et al . 46 . (C and D) Interstudy validation plots with a single dose of 8 mg and 16 mg SL BUP, respectively, as observed by Harris et al . 47 .

Techniques: