scholarly journals A mechanistic pharmacokinetic model with drug and antidrug antibody interplay, and its application for assessing the impact of immunogenicity response on bioequivalence testing

2020 ◽  
Vol 86 (11) ◽  
pp. 2182-2191
Author(s):  
Kai H. Liao ◽  
Chandrasekhar Udata ◽  
Donghua Yin ◽  
K. Lea Sewell ◽  
Constantino Kantaridis ◽  
...  
Keyword(s):  
Pharmacokinetic Model ◽  
Antidrug Antibody ◽  
Bioequivalence Testing ◽  
The Impact

Investigation of the impact of pharmacokinetic variability and uncertainty on risks predicted with a pharmacokinetic model for chloroform

Toxicology ◽  
1996 ◽  
Vol 111 (1-3) ◽  
pp. 289-303 ◽  
Author(s):  
Bruce C. Allen ◽  
Tammie R. Covington ◽  
Harvey J. Clewell
Keyword(s):  
Pharmacokinetic Model ◽  
Pharmacokinetic Variability ◽  
The Impact

scholarly journals Pharmacodynamics of Gatifloxacin against Streptococcus pneumoniae in an In Vitro Pharmacokinetic Model: Impact of Area under the Curve/MIC Ratios on Eradication

2002 ◽  
Vol 46 (1) ◽  
pp. 69-74 ◽  
Author(s):  
Philip D. Lister
Keyword(s):  
Streptococcus Pneumoniae ◽  
Peak Concentration ◽  
Pharmacokinetic Model ◽  
Area Under The Curve ◽  
Logarithmic Phase ◽  
Pharmacokinetic Models ◽  
Elimination Half ◽  
The Impact ◽  
Similar Peak

ABSTRACT Previous studies have demonstrated that fluoroquinolone area under the curve (AUC)/MIC ratios of 30 to 50 are sufficient to eradicate pneumococci from in vitro pharmacokinetic models (IVPMs). However, more systematic studies of the impact of AUC/MIC ratios on the antipneumococcal activities of fluoroquinolones are needed. In the present study, a two-compartment IVPM was used to evaluate the impact of AUC/MIC ratios on the pharmacodynamics of gatifloxacin against four strains of Streptococcus pneumoniae. Gatifloxacin MICs were 0.4 to 1 μg/ml, whereas levofloxacin MICs were 1.8 to 3.2 μg/ml. Since both peak concentration/MIC (peak/MIC) and AUC/MIC ratios affect fluoroquinolone pharmacodynamics, logarithmic-phase cultures (5 × 107 CFU/ml) were exposed to gatifloxacin at constant peak/MIC ratios of 2:1 to 3:1 at 0 and 24 h, elimination half-lives were varied to provide a range of AUC/MIC ratios, and changes in viable counts were measured over 30 h. As a comparison, levofloxacin was evaluated at similar peak/MIC ratios and at AUC/MIC ratios of 30 to 38. For each strain, killing rates through 4 to 8 h were similar since peak/MIC ratios were kept constant. However, continued killing and eradication were observed only when gatifloxacin AUC/MIC ratios were 27 to 48. Levofloxacin also provided eradication. In contrast, substantial regrowth was observed in most experiments when gatifloxacin AUC/MIC ratios were 9 to 24. These data provide further support that fluoroquinolone AUC/MIC ratios of approximately 30 or higher can be sufficient for eradication of pneumococci from IVPMs. Furthermore, the overall impact of the AUC/MIC ratio was not influenced by the strain evaluated or its susceptibility to gatifloxacin. Further studies with other fluoroquinolones and pneumococci that exhibit wider ranges of susceptibilities are warranted. In addition, similar studies with higher peak/MIC ratios are needed to better define the impact of AUC/MIC ratios and peak/MIC ratios on the antipneumococcal pharmacodynamics of fluoroquinolones.

Use of a simple pharmacokinetic model to study the impact of breast-feeding on infant and toddler body burdens of PCB 153, BDE 47, and DDE

Chemosphere ◽  
2017 ◽  
Vol 185 ◽  
pp. 1081-1089 ◽  
Author(s):  
Matthew Lorber ◽  
Leisa-Maree L. Toms
Keyword(s):  
Breast Feeding ◽  
Pharmacokinetic Model ◽  
The Impact

A Pharmacokinetic Model for Evaluating the Impact of Hepatic and Intestinal First-Pass Loss of Saquinavir in the Rat

2010 ◽  
Vol 39 (2) ◽  
pp. 294-301 ◽  
Author(s):  
R. Lledó-García ◽  
A. Nácher ◽  
V. G. Casabó ◽  
M. Merino-Sanjuán
Keyword(s):  
Pharmacokinetic Model ◽  
First Pass ◽  
The Impact

Population Pharmacokinetic Model to Assess the Impact of Disease State on Thalidomide Pharmacokinetics

2019 ◽  
Vol 60 (1) ◽  
pp. 67-74
Author(s):  
Allison Gaudy ◽  
Renfang Hwang ◽  
Maria Palmisano ◽  
Nianhang Chen
Keyword(s):  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Disease State ◽  
Population Pharmacokinetic ◽  
The Impact

scholarly journals Influence of the OATP Polymorphism on the Population Pharmacokinetics of Methotrexate in Chinese Patients

2019 ◽  
Vol 20 (7) ◽  
pp. 592-600 ◽  
Author(s):  
Zhiqi Wang ◽  
Nan Zhang ◽  
Chaoyang Chen ◽  
Shuqing Chen ◽  
Junyu Xu ◽  
...  
Keyword(s):  
Pharmacokinetic Model ◽  
Genetic Factors ◽  
Plasma Concentrations ◽  
Chinese Patients ◽  
Estimation Methods ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Mixed Effect ◽  
The Impact

Background: The Pharmacokinetics of Methotrexate (MTX) has been reported to show significant intersubject variability. MTX is metabolized by SHMT1 and transported by OATP1B1 and OATP1B3 both of which show genetic polymorphisms. The non-genetic and genetic factors may influence the pharmacokinetics of MTX. Objective: This study aimed to determine the pharmacokinetic parameters of MTX in Chinese patients and to investigate the effect of various non-genetic factors and genetic variants of OATP1B1, OATP1B3 on MTX’s pharmacokinetics. Method: MTX concentration and clinical characteristics data were collected from 71 rheumatoid arthritis patients. For each patient, SLC19A1, SHMT1, OATP1B1, and OATP1B3 genotyping were tested. Population pharmacokinetic analysis was performed by Nonlinear Mixed-Effect Modeling (NONMEM). MTX pharmacokinetic properties analysis was executed using the one-compartment pharmacokinetic model which incorporated first-order conditional estimation methods with interaction. Besides, the impact of genetic factors and demographic factors on MTX disposition were explored. Results: All the genotypes of steady-state plasma concentrations and OATP1B1 rs4149056, OATP1B1 rs2306283, and OATP1B3 rs7311358 were determined. The detected blood drug concentration reached the standard. Genotypes were all measured. At the same time, the population pharmacokinetic model of methotrexate was obtained CL(L·h-1) =8.25× e0.167× SNP (SNP: SLCO1B1 388A/A=3; SLCO1B1 388A/G=2; SLCO1B1 388G/G=1); V(L)= 32.8; Ka(h- 1)=1.69. Conclusion: : In our study, it was showed that OATP1B1-388 G>A SNP had a significant effect on CL/F. The factor should be considered when determining MTX dosing. However, prospective studies with a large number of participants are needed to validate the results of this study.

scholarly journals Impact of gender, albumin, and CYP2C19 polymorphisms on valproic acid in Chinese patients: a population pharmacokinetic model

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052095228
Author(s):  
Jinlin Guo ◽  
Yayu Huo ◽  
Fang Li ◽  
Yuanping Li ◽  
Zhaojun Guo ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Volume Of Distribution ◽  
Chinese Patients ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data ◽  
Mixed Effect ◽  
First Order ◽  
The Impact

Objective This prospective study aimed to establish the valproic acid (VPA) population pharmacokinetic model in Chinese patients and realise personalised medication on the basis of population pharmacokinetics. Methods The patients’ clinical information and VPA plasma concentrations were collected from The General Hospital of Taiyuan Iron & Steel (Group) Corporation (TISCO). Nonlinear mixed-effect modelling was used to build the population pharmacokinetic model. To characterise the pharmacokinetic data, a one-compartment pharmacokinetic model with first-order absorption and elimination was used. The first-order conditional estimation with η-ε interaction was applied throughout the model-developing procedure. The absorption rate constant (Ka) was fixed at 2.38 hour−1, and the impact of covariates on clearance and apparent volume of distribution were also explored. Medical records of 60 inpatients were reviewed prospectively and the objective function value (OFV) of the base model and final model were 851.813 and 817.622, respectively. Results Gender was identified as the covariate that had a significant impact on the volume of distribution, and albumin and CYP2C19 genotypes influenced clearance. Conclusion Bootstrap and VPC indicated that a reliable model had been developed that was based on the simulation results, and a simple-to-use dosage regimen table was created to guide clinicians for VPA drug dosing.

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