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Ciprofloxacin Model

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    Hands-On Model  building exercise –  Stepwise Solution -  Disclaimer: Examples described herein have been designed to teach physiologically-based pharmacokinetic / pharmacodynamic (PBPK/PD) modeling with PK-Sim ®  and MoBi ® . Cases may have been simplified to focus on relevant didactic aspects and may not necessarily describe the best model variant.  Exercise  –  Setting up a simple PBPK Model Background Ciprofloxacin is an antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra-abdominal infections, certain type of infectious diarrhea, respiratory tract infections, skin infections, typhoid fever, and urinary tract infections, among others. For some infections it is used in addition to other antibiotics. It can be taken orally or used intravenously. Objectives   o   Learn to set up an (adult model) simulation for Ciprofloxacin and compare simulation to observed data. o   Create building blocks relevant to set up a per os (PO) simulation: administration protocol and formulation o   Parameters predictive for intestinal absorption. o   Learn to compare simulations. Open Ex_PBPK _1.pksim5 .  Set up a Simulation    Make yourself familiar with the given Individual , Compound  and Administration   Protocol .    Click “ Simulation ” in the “ Create ”  Group   of the “ Modeling ” ribbon tab.    Create the Simulation   “ Caucasian ” using the predefined building blocks   o   Individual : “ Healthy Individual Cipro ”   next o   Compound : “ Ciprofloxacin ” , leave Partition coefficients  and Cellular permeabilities   on “ PKSim Standard ”, Choose “ Measurement from Drug Bank ” for Lipophilicity   and select “ Fitted ” for Specific intestinal permeability .   next o   Select  processes :  CYP1A2    “ CYP1A2-DB ” , Renal Clearances “ NONE ” , Glomerular Filtration “GFR” , Biliary Clearance “BC”   o   Administration Protocol : “Dav i s 200iv”   o   Events   nothing to do   click OK      Have a look at the “ Settings ”  in the appearing simulation (output intervals and time-point resolution).    Click “ Run ” in the “ Simulation ” group of the “ Run & Analyze ” ribbon tab.    Select the predefined “ Peripheral Venous Blood Plasma Ciprofloxacin Concentration ” and click “ OK ”.      The simulation is processed.    Drag & Drop the Data “ Davis et al 100mg iv ” into the Results Window .

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Oct 8, 2019
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