Journal: Antibiotics

Article Title: A Minimal Physiologically Based Pharmacokinetic Model to Characterize CNS Distribution of Metronidazole in Neuro Care ICU Patients

doi: 10.3390/antibiotics11101293

Figure Lengend Snippet: Visual predictive checks of the final PBPK model for unbound metronidazole concentrations in plasma, brain dialysates after correction by in vivo probe recovery (Brain Dialysate ) and collection bag of the EVD (CSF EVD ). Circles represent observed data; the solid lines correspond to the median and the grey-shaded area depict the 90% prediction interval delimited by the 5th and 95th percentiles (dashed lines) for 1000 simulated profiles.

Article Snippet: By comparison, the value given by Simcyp and used in the PBPK model (6.4 L/h) was similar to the value calculated using previously reported equations from the literature (6.3 L/h) [ ] but slightly higher than the value obtained from PK-Sim, another PBPK platform (2.4 L/h).

Techniques: Clinical Proteomics, In Vivo

Journal: Antibiotics

Article Title: A Minimal Physiologically Based Pharmacokinetic Model to Characterize CNS Distribution of Metronidazole in Neuro Care ICU Patients

doi: 10.3390/antibiotics11101293

Figure Lengend Snippet: Simulation of the impact of increased passive diffusion clearances, PS ECF/CSF ( a ), increased brain ECF volume, V ECF ( b ) and reduced cerebral blood flow, Q brain ( c ) on CNS PK profiles of metronidazole after administration of a single dose of 500 mg using the minimal PBPK model. The plots were stratified by CNS compartment (panels).

Article Snippet: By comparison, the value given by Simcyp and used in the PBPK model (6.4 L/h) was similar to the value calculated using previously reported equations from the literature (6.3 L/h) [ ] but slightly higher than the value obtained from PK-Sim, another PBPK platform (2.4 L/h).

Techniques: Diffusion-based Assay

Journal: Antibiotics

Article Title: A Minimal Physiologically Based Pharmacokinetic Model to Characterize CNS Distribution of Metronidazole in Neuro Care ICU Patients

doi: 10.3390/antibiotics11101293

Figure Lengend Snippet: Schematic representation of metronidazole minimal PBPK model: the values of the parameters in color are fixed and those of the parameters in black are estimated. Parameters in blue are system-specific parameters, the parameter in green is determined experimentally, and parameters in red are parameters derived from system- and drug-specific parameters. The dashed line represents the blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier (BCSFB). ECF: extracellular fluid, CSF: cerebrospinal fluid, CO: cardiac output, Q brain : cerebral blood flow, Q bulk : bulk flow, Q sink : sink flow, Q EVD : flow of the external ventricular drain, PS ECF : rate of bidirectional passive unbound drug transfer across the BBB, PS CSF : rate of bidirectional passive unbound drug transfer across the BCSFB, V blood : blood volume, V tissue : volume of non-CNS tissue compartment, V brain,vasc : brain vascular volume, V ECF : ECF brain tissue volume, V CSF : cranial CSF volume, fd: fraction of CO going to the non-CNS tissue compartment, K p : unbound tissue to blood partition coefficient, CL: total blood clearance.

Article Snippet: By comparison, the value given by Simcyp and used in the PBPK model (6.4 L/h) was similar to the value calculated using previously reported equations from the literature (6.3 L/h) [ ] but slightly higher than the value obtained from PK-Sim, another PBPK platform (2.4 L/h).

Techniques: Derivative Assay