Research ArticlesPharmacodynamic Modeling of Bacterial Kinetics: β‐Lactam Antibiotics against Escherichia colj
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Pharmacokinetic/pharmacodynamic models for time courses of antibiotic effects
2022, International Journal of Antimicrobial AgentsCitation Excerpt :Their proportion in the total bacterial population was estimated, together with separate values of, for example, kgrowth, EC50 and Emax. Li et al. assumed a gradual first-order transition of bacteria from a susceptible state to a resistant state exhibiting a different growth (and no death) rate (Fig. 2f) [26]. PKPD models assuming a drug-induced gradually developing resistance often included a time-dependent decline in kgrowth or Emax.
Translational PK/PD of anti-infective therapeutics
2016, Drug Discovery Today: TechnologiesCitation Excerpt :More than one differential equation is used simultaneously with each equation representing one bacterial subpopulation (often with different drug susceptibilities) [34]. A variation of the subpopulation model is one in which new drug resistant mutants are formed from the growing subpopulation with a first-order mutation rate during the experiment resulting in regrowth [35]. A modification of the sub-population approach could potentially be used to facilitate development of new generation anti-infectives which do not necessarily kill the bacteria.
Pharmacokinetic/pharmacodynamic modeling for concentration-dependent bactericidal activity of a bicyclolide, modithromycin
2014, Journal of Pharmaceutical SciencesCitation Excerpt :Pharmacokinetic (PK)/pharmacodynamic (PD) analysis plays an important role in drug development and clinical pharmacotherapy of various kinds of drugs.1 2 3 For antibiotics, several PK/PD models have been proposed to explain bacterial count profiles in in vitro and in vivo experiments.4 5 6 7 8 9 10 11 12 13 14 For the analyses of bactericidal kinetics in in vitro time-kill experiments, we developed a drug–bacterium interaction model of β-lactams10 based on a logistic growth function15 with two cellular compartments9 16 and a saturable killing model.6 07
Pharmacokinetic/pharmacodynamic modeling and simulation to determine effective dosage regimens for doripenem
2010, Journal of Pharmaceutical SciencesPharmacokinetic-pharmacodynamic modeling and simulation for bactericidal effect in an in vitro dynamic model
2008, Journal of Pharmaceutical SciencesCitation Excerpt :Some models are reported in time-kill experiments.6-11 We have already developed a model based on a logistic growth function12 with consideration of two cellular compartments8, 13 and a saturable killing model.10, 14 Because the drug concentration in plasma or at an infection site is continuously changing under in vivo situation, the PK profile of a drug with a certain dosage regimen should be incorporated, and an experimental system called “an in vitro dynamic model” is proposed for this purpose.15-22
Pharmacokinetic-pharmacodynamic modeling and simulation for in vivo bactericidal effect in murine infection model
2008, Journal of Pharmaceutical SciencesCitation Excerpt :In this model, two distinct hypothetical compartments are assumed for the bacteria because we confirmed that the inclusion of x2 compartment is statistically significant for the analysis of the in vitro data.10 These two compartments might correspond to the cells of the growth phase sensitive to drugs and the resting cells insensitive to drugs, respectively, as described in other articles.12, 13 Initial conditions for Eqs. (2–5) are: x1(0) = x0, x2(0) = 0, A1(0) = dose, A2(0) = 0, and therefore C(0) = 0, where x0 is the bacterial counts at 0 h. fu is an unbound fraction given by 1 − fb, where fb is a bound fraction and the values are 0.252, 0.189, and 0.025 for DRPM, MEPM, and IPM by an ultrafiltration method for the murine serum protein (unpublished data).