An integrative population pharmacokinetics approach to the characterization of the effect of hepatic impairment on clobazam pharmacokinetics

2015 ◽  
Vol 56 (2) ◽  
pp. 213-222 ◽  
Author(s):  
Dwain Tolbert ◽  
Ihor Bekersky ◽  
Hui-May Chu ◽  
Ene I. Ette
Keyword(s):  
Population Pharmacokinetics ◽  
Hepatic Impairment

scholarly journals Population pharmacokinetics of methadone in opiate users: characterization of time‐dependent changes

1999 ◽  
Vol 48 (1) ◽  
pp. 43-52 ◽  
Author(s):  
Amin Rostami‐Hodjegan ◽  
Kim Wolff ◽  
Alastair W. M. Hay ◽  
Duncan Raistrick ◽  
Robert Calvert ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Time Dependent

scholarly journals Using pharmacokinetics to individualize hemophilia therapy

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 595-604 ◽  
Author(s):  
Alfonso Iorio
Keyword(s):  
Population Pharmacokinetics ◽  
Interindividual Variability ◽  
Clinical Care ◽  
Activity Level ◽  
Clotting Factor ◽  
Factor Activity ◽  
Individualized Dosing ◽  
Case Basis ◽  
Individual Pharmacokinetics

Abstract Prevention and treatment of bleeding in hemophilia requires that plasma clotting factor activity of the replaced factor exceeds a defined target level. Most clinical decisions in hemophilia are based on implicit or explicit application of pharmacokinetic measures. The large interindividual variability in pharmacokinetics of factor concentrates suggests that relying on the average pharmacokinetic characteristics of factor concentrates would not allow optimizing the treatment of individual patients; for example, adjusting the frequency of infusions and targeting a specific clotting factor activity level on a case-by-case basis. However, individual pharmacokinetic profiles are seldom assessed as part of routine clinical care. Population pharmacokinetics provide options for precise and convenient characterization of pharmacokinetics characteristics of factor concentrates, simplified individual pharmacokinetic profiling, and individualized dosing. Population pharmacokinetics allow for the incorporation of determinants of interpatient variability and reduces the need for extensive postinfusion plasma sampling. Barriers to the implementation of population pharmacokinetics are the need for concentrate-specific pharmacokinetic models, Bayesian calculation power, and specific expertise for production, validation, and appraisal of forecasted estimates. Population pharmacokinetics provide an important theoretical and practical contribution to tailoring the treatment of hemophilia. The need remains for prospective exploration of the clinical impact of tailoring hemophilia treatment based on individual pharmacokinetics, and for the systematic validation of existing software solutions and concentrate-specific models.

scholarly journals Population Pharmacokinetics of Single-Dose Riociguat in Patients with Renal or Hepatic Impairment

2016 ◽  
Vol 6 (1_suppl) ◽  
pp. S75-S85 ◽  
Author(s):  
Soundos Saleh ◽  
Corina Becker ◽  
Reiner Frey ◽  
Wolfgang Mück
Keyword(s):  
Single Dose ◽  
Population Pharmacokinetics ◽  
Hepatic Impairment

scholarly journals Population pharmacokinetics of afatinib and exposure-safety relationships in Japanese patients with EGFR mutation-positive non-small cell lung cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Keiko Nakao ◽  
Shinji Kobuchi ◽  
Shuhei Marutani ◽  
Ayano Iwazaki ◽  
Akihiro Tamiya ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Population Pharmacokinetics ◽  
Cell Lung Cancer ◽  
Hepatic Impairment ◽  
Plasma Concentrations ◽  
Small Cell ◽  
Small Cell Lung ◽  
Multiple Dosing ◽  
Population Pk

AbstractTo investigate the exposure–safety relationships of afatinib in Japanese population, we performed population pharmacokinetics (PK) analysis of afatinib in Japanese advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutation. Plasma samples were collected at 0.5–1, 2–3, 8–12, and 24 h after oral afatinib (40 mg) administration on day 1 and day 8. Plasma afatinib concentrations were determined using high-performance liquid chromatography. Data was analyzed following the population approach and using the software Phoenix® NLMETM Version 7.0 software (Certara USA, Inc., Princeton, NJ, USA). From 34 patients, a total of 354 afatinib plasma concentration values were available for the population PK analysis. Significant covariates in the population PK model included aspartate aminotransferase and creatinine clearance on CL/F, and age and body mass index on V/F. Results of simulation based on final PK model indicated that hepatic impairment had a significant effect on afatinib levels in plasma after multiple dosing. Afatinib trough plasma concentrations on day 8 were higher in patients with adverse events of grade 3 or higher. The population PK analysis showed that hepatic impairment affected afatinib PK parameters and contributed to the high inter-patient variability and high plasma concentrations of afatinib following multiple treatments.

scholarly journals Characterization of the Effect of Hepatic Impairment on Upadacitinib Pharmacokinetics

2019 ◽  
Vol 59 (9) ◽  
pp. 1188-1194 ◽  
Author(s):  
Sheryl Trueman ◽  
Mohamed‐Eslam F. Mohamed ◽  
Tian Feng ◽  
Ana Paula Lacerda ◽  
Thomas Marbury ◽  
...  
Keyword(s):  
Hepatic Impairment

scholarly journals Analysis of FDA Oncology Approvals on the Characterization of Hepatic Impairment Effect and Dosing Recommendations

2021 ◽  
Author(s):  
Derek Z. Yang ◽  
Ali Alhadab ◽  
Kourosh Parivar ◽  
Diane D. Wang ◽  
Mohamed Elmeliegy
Keyword(s):  
Hepatic Impairment

Morphological Characterization of Mycobacteriophage R1

1974 ◽  
Vol 32 ◽  
pp. 254-255
Author(s):  
B. L. Soloff ◽  
T. A. Rado
Keyword(s):  
Carbon Source ◽  
Stationary Phase ◽  
Growth Phase ◽  
Minimal Medium ◽  
Morphological Characterization ◽  
Logarithmic Growth Phase ◽  
Complete Lysis ◽  
Lysogenic Culture ◽  
Logarithmic Growth

Mycobacteriophage R1 was originally isolated from a lysogenic culture of M. butyricum. The virus was propagated on a leucine-requiring derivative of M. smegmatis, 607 leu−, isolated by nitrosoguanidine mutagenesis of typestrain ATCC 607. Growth was accomplished in a minimal medium containing glycerol and glucose as carbon source and enriched by the addition of 80 μg/ ml L-leucine. Bacteria in early logarithmic growth phase were infected with virus at a multiplicity of 5, and incubated with aeration for 8 hours. The partially lysed suspension was diluted 1:10 in growth medium and incubated for a further 8 hours. This permitted stationary phase cells to re-enter logarithmic growth and resulted in complete lysis of the culture.

AEM analysis of crystallization in Ti-based amorphous alloys

1983 ◽  
Vol 41 ◽  
pp. 270-271
Author(s):  
A.R. Pelton ◽  
A.F. Marshall ◽  
Y.S. Lee
Keyword(s):  
Magnetic Properties ◽  
Amorphous Alloys ◽  
Amorphous Materials ◽  
Isothermal Annealing ◽  
Amorphous Matrix ◽  
Nucleation And Growth ◽  
Current Interest ◽  
Amorphous Films ◽  
Electrical And Magnetic Properties

Amorphous materials are of current interest due to their desirable mechanical, electrical and magnetic properties. Furthermore, crystallizing amorphous alloys provides an avenue for discerning sequential and competitive phases thus allowing access to otherwise inaccessible crystalline structures. Previous studies have shown the benefits of using AEM to determine crystal structures and compositions of partially crystallized alloys. The present paper will discuss the AEM characterization of crystallized Cu-Ti and Ni-Ti amorphous films.Cu60Ti40: The amorphous alloy Cu60Ti40, when continuously heated, forms a simple intermediate, macrocrystalline phase which then transforms to the ordered, equilibrium Cu3Ti2 phase. However, contrary to what one would expect from kinetic considerations, isothermal annealing below the isochronal crystallization temperature results in direct nucleation and growth of Cu3Ti2 from the amorphous matrix.

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