full pbpk distribution model  (Simcyp)

Journal: British journal of clinical pharmacology

Article Title: Physiologically-based pharmacokinetic modelling of long-acting injectable cabotegravir and rilpivirine in pregnancy.

doi: 10.1111/bcp.16006

Figure Lengend Snippet: FIGURE 1 (A) Schematic pregnancy physiologically-based pharmacokinetic (PBPK) model diagram illustrating organs and tissues as compartments, and blood flows as (blue/red) arrows. IM, intramuscular. (B) Illustration of the foetal compartment as modelled within the uterus.

Article Snippet: A full-body adult PBPK model was developed in SimBiology®, a product of MATLAB® software, version R2019a (MathWorks, Natick, USA, 2019).

Techniques:

Journal: Frontiers in Pharmacology

Article Title: A minimal PBPK model to accelerate preclinical development of drugs against tuberculosis

doi: 10.3389/fphar.2023.1272091

Figure Lengend Snippet: A visual representation of the minimal PBPK model. The model consists of nine compartments, eight of which describing: arterial and venous blood, gut, splenic, liver, lung, kidney, and the lumped compartment “other”. In addition, there is a compartment to account for the oral dose disposition. Black lines represent exchange between the compartments. Grey lines represent the first-order clearance.

Article Snippet: The model was benchmarked in terms of computational time with a reference full-body PBPK model available in Matlab SimBiology ( ; ; ).

Techniques:

Journal: CPT: Pharmacometrics & Systems Pharmacology

Article Title: Development and application of neonatal physiology‐based pharmacokinetic models of amikacin and fosfomycin to assess pharmacodynamic target attainment

doi: 10.1002/psp4.13097

Figure Lengend Snippet: Visual validation of fosfomycin adult, pediatric, and neonatal PBPK models. The black solid line indicates the mean systemic concentration predicted by the PBPK model, with gray solid lines indicating 5th and 95th centiles, from 100 simulated individuals for each validation. The overlying symbols indicate observed concentrations from the test dataset. (a) Adult fosfomycin PBPK model simulating a 50 mg/kg i.v. bolus in adult healthy volunteers, with overlaid individual observed data from Segre et al. ¹⁷ (b) Pediatric fosfomycin PBPK model simulating a 25 mg/kg i.v. bolus in children aged 3–8 years, with overlaid population mean observed data from Guggenbichler et al. ²⁷ (c) Initial neonatal fosfomycin PBPK model simulating a 100 mg/kg i.v. bolus in neonates aged 0–23 days, with overlaid population mean observed data from Kane et al. ⁸ (d) Adjusted neonatal fosfomycin PBPK model (with Kp scalar of 1.2) simulating 100 mg/kg i.v. bolus in neonates aged 0–23 days, with overlaid population mean observed data from Kane et al. ⁸ PBPK, physiologically‐based pharmacokinetic.

Article Snippet: Using the physical–chemical properties and pharmacological parameters for fosfomycin, which is an ampholyte (Table ), the best performing tissue distribution prediction was a full PBPK model using the Gaohua model (Model 3 in Simcyp), which predicted a steady‐state volume of distribution ( V ss ) of 0.24 L/kg.

Techniques: Biomarker Discovery, Concentration Assay

Journal: CPT: Pharmacometrics & Systems Pharmacology

Article Title: Development and application of neonatal physiology‐based pharmacokinetic models of amikacin and fosfomycin to assess pharmacodynamic target attainment

doi: 10.1002/psp4.13097

Figure Lengend Snippet: Visual validation of amikacin adult, pediatric, and neonatal PBPK models. The solid line indicates the mean systemic concentration predicted by the PBPK model, with gray solid lines indicating 5th and 95th centiles, from 100 simulated individuals for each validation. The overlying symbols indicate observed concentrations from the test dataset. (a) Adult amikacin PBPK model simulating a 7.5 mg/kg i.v. infusion over 30 min in adult healthy volunteers, with overlaid population mean observed data from Garraffo et al. (b) Pediatric amikacin PBPK model simulating a 5 mg/kg i.v. infusion over 60 min in children aged 1–16 years, with overlaid population mean observed data from Cleary et al. ³⁵ (c) Neonatal fosfomycin PBPK model simulating a 3 mg/kg i.v. infusion over 30 min in neonates aged 2 – 8 days using a Kp scaler of 0.17, with overlaid individual observed data from Nishimura et al. ³⁶ (d) As panel (c), but using a PBPK model with a Kp scalar of 0.325. PBPK, physiologically‐based pharmacokinetic.

Article Snippet: Using the physical–chemical properties and pharmacological parameters for fosfomycin, which is an ampholyte (Table ), the best performing tissue distribution prediction was a full PBPK model using the Gaohua model (Model 3 in Simcyp), which predicted a steady‐state volume of distribution ( V ss ) of 0.24 L/kg.

Techniques: Biomarker Discovery, Concentration Assay

Journal: CPT: Pharmacometrics & Systems Pharmacology

Article Title: Development and application of neonatal physiology‐based pharmacokinetic models of amikacin and fosfomycin to assess pharmacodynamic target attainment

doi: 10.1002/psp4.13097

Figure Lengend Snippet: PBPK model output from a simulation of 1000 term neonates aged 0–7 days receiving fosfomycin 100 mg/kg i.v. bolus q12h (a) and amikacin 15 mg/kg i.v. bolus q24h (b), with simulation data sampled every 5 min. The variable C max values are due, in part, to the simulated ontogeny and growth of each individual neonate over the simulation time period. C max , maximum plasma concentration; PBPK, physiologically‐based pharmacokinetic.

Article Snippet: Using the physical–chemical properties and pharmacological parameters for fosfomycin, which is an ampholyte (Table ), the best performing tissue distribution prediction was a full PBPK model using the Gaohua model (Model 3 in Simcyp), which predicted a steady‐state volume of distribution ( V ss ) of 0.24 L/kg.

Techniques: Clinical Proteomics, Concentration Assay

Journal: CPT: Pharmacometrics & Systems Pharmacology

Article Title: Development and application of neonatal physiology‐based pharmacokinetic models of amikacin and fosfomycin to assess pharmacodynamic target attainment

doi: 10.1002/psp4.13097

Figure Lengend Snippet: Probability of target attainment for the fosfomycin/amikacin combination breakpoint described in Darlow et al. ⁶ across a range of fosfomycin and amikacin MICs for each of the PBPK model simulations in term neonates.

Article Snippet: Using the physical–chemical properties and pharmacological parameters for fosfomycin, which is an ampholyte (Table ), the best performing tissue distribution prediction was a full PBPK model using the Gaohua model (Model 3 in Simcyp), which predicted a steady‐state volume of distribution ( V ss ) of 0.24 L/kg.

Techniques: