scholarly journals Importance of Exposure-Response Information to Optimal Dosing in Clinical Trialsa

2018 ◽  
Vol 5 (4) ◽  
Author(s):  
Suliman Al Fayoumi
Keyword(s):  
Exposure Response ◽  
Response Information ◽  
Optimal Dosing

scholarly journals Exposure–response modelling approaches for determining optimal dosing rules in children

2020 ◽  
Vol 29 (9) ◽  
pp. 2583-2602
Author(s):  
Ian Wadsworth ◽  
Lisa V Hampson ◽  
Björn Bornkamp ◽  
Thomas Jaki
Keyword(s):  
Recursive Partitioning ◽  
Age Groups ◽  
In Vitro Study ◽  
Model Parameters ◽  
Response Model ◽  
B Splines ◽  
Model Based ◽  
Exposure Response ◽  
Optimal Dosing

Within paediatric populations, there may be distinct age groups characterised by different exposure–response relationships. Several regulatory guidance documents have suggested general age groupings. However, it is not clear whether these categorisations will be suitable for all new medicines and in all disease areas. We consider two model-based approaches to quantify how exposure–response model parameters vary over a continuum of ages: Bayesian penalised B-splines and model-based recursive partitioning. We propose an approach for deriving an optimal dosing rule given an estimate of how exposure–response model parameters vary with age. Methods are initially developed for a linear exposure–response model. We perform a simulation study to systematically evaluate how well the various approaches estimate linear exposure–response model parameters and the accuracy of recommended dosing rules. Simulation scenarios are motivated by an application to epilepsy drug development. Results suggest that both bootstrapped model-based recursive partitioning and Bayesian penalised B-splines can estimate underlying changes in linear exposure–response model parameters as well as (and in many scenarios, better than) a comparator linear model adjusting for a categorical age covariate with levels following International Conference on Harmonisation E11 groupings. Furthermore, the Bayesian penalised B-splines approach consistently estimates the intercept and slope more accurately than the bootstrapped model-based recursive partitioning. Finally, approaches are extended to estimate Emax exposure–response models and are illustrated with an example motivated by an in vitro study of cyclosporine.

Application of Clinical Pharmacology Principles in Drug Development of Modified‐Release Products: Leveraging Exposure‐Response Information to Support Approval

2020 ◽  
Vol 60 (11) ◽  
pp. 1441-1452
Author(s):  
Bilal S. AbuAsal ◽  
Salaheldin S. Hamed ◽  
Mariam A. Ahmed ◽  
Lana Al‐Mansour ◽  
Ramana Uppoor ◽  
...  
Keyword(s):  
Clinical Pharmacology ◽  
Drug Development ◽  
Modified Release ◽  
Exposure Response ◽  
Response Information

Detection of emotional states of OCD patients in an exposure-response prevention therapy scenario

2019 ◽  
Author(s):  
Kaajal Gupta ◽  
Anzar Zulfiqar ◽  
Pushpa Ramu ◽  
Tilak Purohit ◽  
V. Ramasubramanian
Keyword(s):  
Response Prevention ◽  
Emotional States ◽  
Exposure Response ◽  
Prevention Therapy ◽  
Exposure Response Prevention

Automatic monitoring of denitrification rates and capacities in activated sludge processes using fluorescence or redox potential

1998 ◽  
Vol 37 (12) ◽  
pp. 121-129 ◽  
Author(s):  
S. Isaacs ◽  
Terry Mah ◽  
S. K. Maneshin
Keyword(s):  
Biological Activity ◽  
Activated Sludge ◽  
Redox Potential ◽  
Treatment Plant ◽  
Automatic Monitoring ◽  
Organic Substrate ◽  
Anoxic Zone ◽  
Optimal Dosing ◽  
Denitrifying Microorganisms ◽  
Activated Sludge Processes

A novel method is described to automatically estimate several key parameters affecting denitrification in activated sludge processes: the nitrate concentration, the denitrification capacity, and the maximum (substrate unlimited) and actual denitrification rates. From these, the concentration of active denitrifying microorganisms and the quality of available organic substrate pool can be estimated. Additionally, a modification of the method allows the determination of the efficacy of various carbon substrates to enhance denitrification, and this can be used to determine optimal dosing rates of an external carbon source. The method is based on measurements of either fluorescence or redox potential (ORP) in an isolated mini-reactor, the Biological Activity Meter (BAM), situated in the anoxic zone of the wastewater treatment plant. Advantages of the method are that it is in situ, operating at the same temperature as in the measured anoxic zone, requires no pumps or pipes for mixed liquor sampling, consumes little or no reagents, and uses measurement signals which are instantaneous and low maintenance, one of which provides a direct measure of biological activity.

scholarly journals Comparison of Some Physical Parameters of Whole and Scored Lisinopril and Lisinopril/Hydrochlorthiazide Tablets

2008 ◽  
Vol 8 (4) ◽  
pp. 391-395 ◽  
Author(s):  
Edina Vranić ◽  
Alija Uzunović
Keyword(s):  
Large Scale ◽  
Testing Procedure ◽  
Physical Parameters ◽  
Hardness Testing ◽  
Disintegration Time ◽  
Adequate Dose ◽  
Response Information ◽  
Tablet Splitting ◽  
Good Patient Compliance ◽  
Accepted Practice

Tablets are one of the most popular and preferred solid dosage forms because they can be accurately dosed, easily manufactured and packaged on a large scale, have good physical and chemical stability, and can contribute to good patient compliance given their ease of administration. The ability to match doses to patients depends on the availability of multiple dose sizes and adequate dose-response information. These are not always provided, so splitting of the tablets is sometimes necessary, Tablet splitting is an accepted practice in dispensing medication, It has been used when a dosage form of the required strength is not available commercially. The aim of our study was to compare some physical parameters of whole and scored lisinopril and lisinopril/hydrochlorthiazide tablets and to accept or exclude their influence on the obtaining of required dosage.According to the results obtained, we may conclude that tablets from batch “I” “IL “III” and “IV” satisfied pharmacopeial requirements concerning crushing strength, friability, disintegration time and mass uniformity. The hardness testing showed acceptable reproducibility and indicate that the data variation was primarily from the irreversible changes in the structure of tablet samples. The act of compacting powders stores energy within the tablets, by shifting or compressing the intermolecular bonds within the particles. The tablets have a natural tendency to relax once pressure is removed, and this tendency works against the interparticle bonding formed during compression. Hardness testing procedure causes irreversible changes in this structure.

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