scholarly journals Age, Weight, and CYP2D6 Genotype Are Major Determinants of Primaquine Pharmacokinetics in African Children

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Bronner P. Gonçalves ◽  
Helmi Pett ◽  
Alfred B. Tiono ◽  
Daryl Murry ◽  
Sodiomon B. Sirima ◽  
...  
Keyword(s):  
Parent Compound ◽  
Age Groups ◽  
Artemisinin Resistance ◽  
Community Treatment ◽  
Population Pharmacokinetic ◽  
Cyp2d6 Genotype ◽  
Content Type ◽  
Population Pharmacokinetic Modeling ◽  
African Children ◽  
The Impact

ABSTRACT Low-dose primaquine is recommended to prevent Plasmodium falciparum malaria transmission in areas threatened by artemisinin resistance and areas aiming for malaria elimination. Community treatment campaigns with artemisinin-based combination therapy in combination with the gametocytocidal primaquine dose target all age groups, but no studies thus far have assessed the pharmacokinetics of this gametocytocidal drug in African children. We recruited 40 children participating in a primaquine efficacy trial in Burkina Faso to study primaquine pharmacokinetics. These children received artemether-lumefantrine and either a 0.25- or a 0.40-mg/kg primaquine dose. Seven blood samples were collected from each participant for primaquine and carboxy-primaquine plasma levels determinations: one sample was collected before primaquine administration and six after primaquine administration according to partially overlapping sampling schedules. Physiological population pharmacokinetic modeling was used to assess the impact of weight, age, and CYP2D6 genotype on primaquine and carboxy-primaquine pharmacokinetics. Despite linear weight normalized dosing, the areas under the plasma concentration-time curves and the peak concentrations for both primaquine and carboxy-primaquine increased with age and body weight. Children who were CYP2D6 poor metabolizers had higher levels of the parent compound, indicating a lower primaquine CYP2D6-mediated metabolism. Our data indicate that primaquine and carboxy-primaquine pharmacokinetics are influenced by age, weight, and CYP2D6 genotype and suggest that dosing strategies may have to be reconsidered to maximize the transmission-blocking properties of primaquine. (This study has been registered at ClinicalTrials.gov under registration no. NCT01935882.)

scholarly journals In Silico Investigation of the Decline in Clinical Efficacy of Artemisinin Combination Therapies Due to Increasing Artemisinin and Partner Drug Resistance

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
Sophie G. Zaloumis ◽  
Pengxing Cao ◽  
Saber Dini ◽  
Miles P. Davenport ◽  
Deborah Cromer ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Failure ◽  
In Silico ◽  
Artemisinin Resistance ◽  
Exact Nature ◽  
Artemisinin Derivative ◽  
Combination Therapies ◽  
Content Type ◽  
Artemisinin Derivatives ◽  
The Impact

ABSTRACT Antimalarial treatment currently relies on an artemisinin derivative and a longer-acting partner drug. With the emergence of resistance to the artemisinin derivatives and the potential pressure this exerts on the partner drugs, the impact of resistance to each drug on efficacy needs to be investigated. An in silico exploration of dihydroartemisinin-piperaquine and mefloquine-artesunate, two artemisinin-based combination therapies that are commonly used in Southeast Asia, was performed. The percentage of treatment failures was simulated from a within-host pharmacokinetic-pharmacodynamic (PKPD) model, assuming that parasites developed increasing levels of (i) artemisinin derivative resistance or (ii) concomitant resistance to both the artemisinin derivative and the partner drug. Because the exact nature of how resistant Plasmodium falciparum parasites respond to treatment is unknown, we examined the impact on treatment failure rates of artemisinin resistance that (i) reduced the maximal killing rate, (ii) increased the concentration of drug required for 50% killing, or (iii) shortened the window of parasite stages that were susceptible to artemisinin derivatives until the drugs had no effect on the ring stages. The loss of the ring-stage activity of the artemisinin derivative caused the greatest increase in the treatment failure rate, and this result held irrespective of whether partner drug resistance was assumed to be present or not. To capture the uncertainty regarding how artemisinin derivative and partner drug resistance affects the assumed concentration-killing effect relationship, a variety of changes to this relationship should be considered when using within-host PKPD models to simulate clinical outcomes to guide treatment strategies for resistant infections.

scholarly journals The impact of product presentation on decision-making and purchasing

2019 ◽  
Vol 22 (3) ◽  
pp. 365-380 ◽  
Author(s):  
Rosy Boardman ◽  
Helen McCormick
Keyword(s):  
Decision Making ◽  
Eye Tracking ◽  
Visual Information ◽  
Age Groups ◽  
Target Market ◽  
Consumer Decision Making ◽  
Consumer Decision ◽  
Content Type ◽  
Product Presentation ◽  
The Impact

Purpose This paper aims to investigate how apparel product presentation influences consumer decision-making and whether there are any differences between age groups. Design/methodology/approach A mixed methodology was used including eye-tracking and qualitative in-depth interviews, with a purposive sample of 50 participants between age 20 and 70. Findings A higher number of product presentation features resulted in increased positive visual, cognitive and affective responses as consumers wanted as much visual information as possible to aid decision-making. Images of models attracted the most attention and were the most influential product presentation feature, followed by mannequin images and the zoom function. The 20 s spent much less time viewing and interacting with the product presentation features than middle age groups (30 s-50 s), had minimal fixations on mannequin images and had a much quicker decision-making process than other age groups. Practical implications The research informs retailers which product presentation features are the most effective for their target market to aid consumer decision-making with the aim of reducing returns. Originality/value The paper contributes to the literature by providing more in-depth insights than previous studies into the impact of online product presentation on consumer decision-making by using qualitative research and eye-tracking. The research also explores more product presentation features than previous research and investigates the presentation of apparel products, which are notoriously the most difficult products for consumers to assess online. The research is unique in its exploration of age differences in relation to product presentation features.

Attachment points, team identification and sponsorship outcomes: evidence from the Indian Premier League

2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Giridhar B. Kamath ◽  
Shirshendu Ganguli ◽  
Simon George
Keyword(s):  
Structural Equation ◽  
Group Analysis ◽  
Age Groups ◽  
Team Identification ◽  
Age And Gender ◽  
Content Type ◽  
Behavioural Intentions ◽  
Premier League ◽  
And Gender ◽  
The Impact

PurposeThis paper tests and validates a conceptual model linking the attachment points, team identification, attitude towards the team sponsors and the behavioural intentions in the context of Indian Premier League (IPL), while testing for the moderating effects of age and gender.Design/methodology/approachData were collected from 1,053 participants through both online and offline survey and then analyzed using exploratory factor analysis (EFA) and structural equation modelling (SEM).FindingsAttachment points influence the formation of team identification, which, in turn, affect the attitude towards the team sponsors. Attitude towards the team sponsors influence the behavioural intentions. Player attachment influences team identification the most. Age and gender have a moderating effect on the constructs of the study. Team identification in females is stronger because of attachment to sports, whereas males have stronger team identification based on player attachment. Males have a stronger intention to spread positive word of mouth (WOM) about sponsor products as compared to the female respondents. The younger age group of less than 21 years has more intention to spread positive WOM compared to the other age groups considered in the study.Practical implicationsThis study contributes towards sports sponsorship research and the paradigms of social identity and attachment theories. Moreover, it will also help the marketers (sponsors) in IPL to strategically market their brands.Originality/valueThis is the first study to investigate the impact of attachment points on sponsorship outcomes in the context of IPL. Further, it is also the first to investigate the purchase intentions and WOM for the team sponsors in IPL. The multi-group analysis results will provide insights into marketers to better understand IPL viewers' segments and their behaviour.

scholarly journals 1558. A Population Pharmacokinetic Model for Posaconazole Intravenous Solution and Oral Powder for Suspension Formulations in Pediatric Patients With Neutropenia

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S569-S569
Author(s):  
Gregory A Winchell ◽  
Rik de Greef ◽  
Rebecca E Wrishko ◽  
Eric Mangin ◽  
Hetty Waskin ◽  
...  
Keyword(s):  
Goodness Of Fit ◽  
Geometric Mean ◽  
Age Groups ◽  
Invasive Fungal Disease ◽  
Population Pharmacokinetic ◽  
Once Daily ◽  
Intravenous Solution ◽  
Backward Procedure ◽  
Using Data ◽  
The Impact

Abstract Background Posaconazole is approved in adults for prophylaxis and treatment of invasive fungal disease. Two formulations that offer weight-based dosing—intravenous (IV) and oral powder for suspension (PFS)—are being evaluated in children. A population pharmacokinetic (popPK) approach was used to characterize and predict the PK exposure of posaconazole PFS and IV formulations in children to identify dosages associated with achieving a target PK of 1200 ng/mL as the mean Cavg and individual Cavg ≥500 ng/mL and <2500 ng/mL in ~90% of patients. Methods A popPK model was developed through nonlinear mixed-effects modeling using data obtained from a trial in children with neutropenia (ClinicalTrials.gov, NCT02452034; Merck protocol, MK-5592-097). Three dose cohorts (3.5, 4.5, and 6 mg/kg/day [≤300 mg/day]) were studied in two age groups (2–<7 years and 7–17 years). Posaconazole IV was administered twice on day 1 then once daily through at least day 10, followed by PFS once daily through day 28 at clinician discretion. A compartmental model, including both formulations, was fit to the data. Model selection was based on the Log-Likelihood Criterion, goodness-of-fit plots, and scientific plausibility. Significance of the covariates was assessed in a stepwise forward inclusion/backward procedure. An additional assessment characterized the impact of different food covariates on bioavailability. Results An open one-compartmental PK model with first-order absorption and estimated bioavailability, as well as allometrically scaled effects of body weight on clearance and volume, adequately described the PK of posaconazole IV and PFS formulations. Model predictions are shown in the Table. Effects of the different food covariates were not statistically significant. Simulations indicated that for the 6-mg/kg/d dose, model-predicted Cavg generally met PK targets. Model-predicted Cavg was ≥500 ng/mL in >90% of subjects in all cohorts. The 1200-ng/mL target geometric mean Cavg was achieved for all but the 2–<7 years cohort receiving the PFS formulation. Conclusion This popPK-based analysis demonstrated that the 6-mg/kg/d dose of IV or PFS posaconazole formulation (≤300 mg/days) is appropriate for children (2–17 years) and that PFS can be administered without regard to food. Disclosures All authors: No reported disclosures.

Factors influencing the choice of financial advisor by women stock investors in Punjab

2017 ◽  
Vol 59 (2) ◽  
pp. 192-201
Author(s):  
Mandeep Kaur ◽  
Tina Vohra
Keyword(s):  
Service Providers ◽  
Age Groups ◽  
Financial Advisors ◽  
Women Clients ◽  
Content Type ◽  
Financial Advisor ◽  
Investment Advisor ◽  
The Impact ◽  
Structured Questionnaire

Purpose The paper aims to attempt to identify the attributes that women look for in their financial advisor and to examine if the choice of attributes of a financial advisor among women investors in Punjab is the same across demographics. The understanding of the attributes that women want in their financial advisor will help the financial advisors to be mindful of the opportunities and the challenges they have to face while working with women investors. Studying the impact of demographics on the choice of the investment advisor would enable the service providers to provide women with services relevant to their unique and individual situations. Design/methodology/approach A pre-tested, well-structured questionnaire was constructed and administered personally, and the responses of 200 women investors were analyzed. The sum of the ranks assigned by women to various attributes determining the choice of a financial advisor was used to find out the most preferred attribute on the basis of which women choose their financial advisor. The Kruskal Wallis test was used to analyze the impact of demographics on the choice of the respondents. Findings The results of the study brought out that the friendliness of the financial advisor, and the quality of advice provided by them are preferred attributes determining the choice of a financial advisor. Along with this, the results also state that the preference for the attribute friendliness and quality of advice is not the same across age groups. The choice of attributes also varies according to the marital status of the respondents. Practical implications The current study will contribute toward a greater understanding of the attributes which are considered important by women while choosing their financial advisor. The study will help the financial advisors to cater to the needs of their women clients. Moreover, the study will also benefit women by bringing about a positive change in the attitude of the financial advisors in favor of them. The greater sensitization of the financial advisors toward their women clients would lead to greater stock market participation among women, thereby benefitting the society. Originality/value The paper is an attempt to identify the attributes that women look for in their financial advisor and to examine if the choice of attributes of a financial advisor among women investors in Punjab is the same across demographics or not. Therefore, the study contributes to the understanding of the investment behavior of women.

scholarly journals Population Pharmacokinetic/Pharmacodynamic Analysis of the Bactericidal Activities of Sutezolid (PNU-100480) and Its Major Metabolite against Intracellular Mycobacterium tuberculosis inEx VivoWhole-Blood Cultures of Patients with Pulmonary Tuberculosis

2014 ◽  
Vol 58 (6) ◽  
pp. 3306-3311 ◽  
Author(s):  
Tong Zhu ◽  
Sven O. Friedrich ◽  
Andreas Diacon ◽  
Robert S. Wallis
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Hollow Fiber ◽  
Ex Vivo ◽  
Parent Compound ◽  
Plasma Concentrations ◽  
Population Pharmacokinetic ◽  
Model Parameters ◽  
Data Set ◽  
Content Type

ABSTRACTSutezolid (PNU-100480 [U-480]) is an oxazolidinone antimicrobial being developed for the treatment of tuberculosis. An active sulfoxide metabolite (PNU-101603 [U-603]), which reaches concentrations in plasma several times those of the parent, has been reported to drive the killing of extracellularMycobacterium tuberculosisby sutezolid in hollow-fiber culture. However, the relative contributions of the parent and metabolite against intracellularM. tuberculosisin vivoare not fully understood. The relationships between the plasma concentrations of U-480 and U-603 and intracellular whole-blood bactericidal activity (WBA) inex vivocultures were examined using a direct competitive population pharmacokinetic (PK)/pharmacodynamic 4-parameter sigmoid model. The data set included 690 PK determinations and 345 WBA determinations from 50 tuberculosis patients enrolled in a phase 2a sutezolid trial. The model parameters were solved iteratively. The median U-603/U-480 concentration ratio was 7.1 (range, 1 to 28). The apparent 50% inhibitory concentration of U-603 for intracellularM. tuberculosiswas 17-fold greater than that of U-480 (90% confidence interval [CI], 9.9- to 53-fold). Model parameters were used to simulatein vivoactivity after oral dosing with sutezolid at 600 mg twice a day (BID) and 1,200 mg once a day (QD). Divided dosing resulted in greater cumulative activity (−0.269 log10per day; 90% CI, −0.237 to −0.293 log10per day) than single daily dosing (−0.186 log10per day; 90% CI, −0.160 to −0.208 log10per day). U-480 accounted for 84% and 78% of the activity for BID and QD dosing, respectively, despite the higher concentrations of U-603. Killing of intracellularM. tuberculosisby orally administered sutezolid is mainly due to the activity of the parent compound. Taken together with the findings of other studies in the hollow-fiber model, these findings suggest that sutezolid and its metabolite act on different mycobacterial subpopulations.

scholarly journals Influence of Experimental Cryptococcal Meningitis in Wistar Rats on Voriconazole Brain Penetration Assessed by Microdialysis

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Izabel Almeida Alves ◽  
Keli Jaqueline Staudt ◽  
Carolina de Miranda Silva ◽  
Graziela de Araujo Lock ◽  
Teresa Dalla Costa ◽  
...  
Keyword(s):  
Cryptococcal Meningitis ◽  
Free Fraction ◽  
Volume Of Distribution ◽  
Time Profile ◽  
Peripheral Compartment ◽  
Population Pharmacokinetic ◽  
Brain Penetration ◽  
Content Type ◽  
Liquid Chromatography Tandem Mass ◽  
The Impact

ABSTRACT To make advances in the treatment of cryptococcal meningitis, it is crucial to know a given drug's free fraction that reaches the biophase. In the present study, we applied microdialysis (μD) as a tool to determine the free levels reached by voriconazole (VRC) in the brains of healthy and Cryptococcus neoformans-infected rats. The infection was induced by the intravenous (i.v.) administration of 1 × 105 CFU of yeast. The dose administered was 5 mg/kg (of body weight) of VRC, given i.v. Plasma and microdialysate samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and LC-UV methods. The free brain/free plasma ratio (fT) and population pharmacokinetic (popPK) analyses were performed to evaluate the impact of infection on PK parameters of the drug. The brain penetration ratio showed an increase on brain exposure in infected animals (fThealthy = 0.85 versus fTinfected = 1.86). The structural PK model with two compartments and Michaelis-Menten (MM) elimination describes the VRC concentration-time profile in plasma and tissue simultaneously. The covariate infection was included in volume of distribution in the peripheral compartment in healthy animals (V 2) and maximum rate of metabolism (VM ). The levels reached in infected tissues were higher than the values described for MIC of VRC for Cryptococccus neoformans (0.03 to 0.5 μg ml−1), indicating its great potential to treat meningitis associated with C. neoformans.

The impact of the motivation for status on consumers’ perceptions of retailer sustainability: the moderating impact of collectivism and materialism

2017 ◽  
Vol 34 (4) ◽  
pp. 292-305 ◽  
Author(s):  
Mertcan Tascioglu ◽  
Jacqueline Kilsheimer Eastman ◽  
Rajesh Iyer
Keyword(s):  
Environmental Sustainability ◽  
Generational Differences ◽  
Age Groups ◽  
Social Sustainability ◽  
Cultural Dimensions ◽  
Future Research ◽  
Bandwagon Effect ◽  
Content Type ◽  
The Impact ◽  
The Relationship

Purpose The purpose of the study is to investigate consumers’ perceptions of status motivations on retailers’ sustainability efforts and whether collectivism and materialism moderate this relationship. Design/methodology/approach A quantitative research methodology using survey data was used. Data were collected by administering questionnaires from millennial respondents (n = 386) from the USA and Turkey. Findings The results show that cultural value (collectivism) and materialism can serve as moderators of the effects of status motivation and sustainability. The findings indicate that the link between status motivation and sustainability perceptions (both environmental and social sustainability) is stronger for more collectivist consumers. In terms of materialism, while it did not moderate the relationship between status motivation and perceptions of environmental sustainability, it did moderate the relationship between status motivation and perceptions of social sustainability, particularly the uniqueness aspect of materialism. Research limitations/implications The stronger link between status motivation and both environmental and social sustainability for collectivists suggests that the bandwagon effect may be impacting their need for status. The stronger link between status motivation and social sustainability for those more materialistic suggests that their need for status may be more impacted by a snob effect as they want to appear unique. The use of college students is a limitation of this study, and future research needs to explore a wider range of age groups to determine if there are generational differences. Additionally, future research could examine other cultural dimensions such as power distance and masculinity versus femininity. Practical implications Findings from this research provide insights for retailers, especially those targeting the status and luxury market when developing their sustainability plans. An interest in sustainability may aid consumers in meeting their need for status, particularly for those status consumers who are more collectivist, as a means to fit in with their group. For more materialistic consumers, retailers may want to focus more on unique social sustainability efforts that are more publicly noticeable. Social implications Social sustainability, a topic not studied as frequently as environmental sustainability, has significant implications for consumers. The findings suggest that the link between status motivation and social sustainability is stronger for collectivists, suggesting a bandwagon effect. Additionally, the authors find that the link between status motivation and social sustainability is stronger for materialists, particularly the uniqueness dimension of materialism, suggesting a snob effect. Originality/value The originality of this study lies in the exploration of how status motivation impacts consumers’ perceptions of retailers’ environmental and social sustainability efforts and if these relationships are moderated by collectivism and materialism. Few studies have examined social sustainability, especially in terms of culture.

Developing teenagers’ role consciousness as “world heritage guardians”

2017 ◽  
Vol 7 (2) ◽  
pp. 179-192 ◽  
Author(s):  
Wenhui Wang ◽  
Yin Zhang ◽  
Jing Han ◽  
Ping Liang
Keyword(s):  
Sustainable Development ◽  
Community Involvement ◽  
Age Groups ◽  
World Heritage ◽  
Three Dimensions ◽  
Structured Interviews ◽  
Content Type ◽  
World Heritage Sites ◽  
Heritage Protection ◽  
The Impact

Purpose As one of the nearest and most important groups of resource guardians, local teenagers are an important force for current and especially future world heritage protection. Nurturing their awareness of world heritage protection is an important way to achieve the sustainable development of world heritage sites (WHS). The purpose of this paper is to present a case study of local teenagers of Tai’an city in China with the aim of examining how they have developed consciousness of their role as “world heritage guardians.” Design/methodology/approach Semi-structured interviews are used to examine the awareness of 15 local teenagers on world heritage protection. The interview results are then qualitatively analyzed by using a systematic coding process. Findings The analysis shows that the formation of the guardianship role is realized through three dimensions: recognition, emotion, and action, which are subjected to role awakening, role identifying, and role strengthening stage by stage. The personal experiences of the interviewees, as well as the impact from surrounding groups both serve to influence the formation of their role as “world heritage guardians.” Research limitations/implications The framework constructed in this study on the development of teenagers’ role consciousness cannot only apply to world heritage and environmental contexts in terms of awareness of the need for conservation, but be used toward behavioral studies of other age groups. Practical implications The findings can be used as a practical guide for school teachers, government officials, and heritage managers to better carry out educational programs in terms of heritage tourism and sustainable development of WHS for teenagers. Originality/value The teenagers’ population is underrepresented in the literature in terms of community involvement with world heritage. This study is meaningful because the focus is on improving local teenagers’ awareness of the value and importance of world heritage and their preservation.

Materialism and compulsive buying behaviour

2018 ◽  
Vol 30 (5) ◽  
pp. 1239-1258 ◽  
Author(s):  
Debasis Pradhan ◽  
D. Israel ◽  
Amit Kumar Jena
Keyword(s):  
Credit Card ◽  
Structural Equation ◽  
Online Survey ◽  
Age Groups ◽  
Likelihood Estimation ◽  
Compulsive Buying ◽  
Measurement Model ◽  
Model Assessment ◽  
Content Type ◽  
The Impact

Purpose The purpose of this paper is to study the impact of materialism on credit card (CC) use and impulsive buying (IB) and compulsive buying (CB) behaviour. Furthermore, it assesses whether CC use and IB behaviour mediate the relationship between materialism and CB behaviour. Design/methodology/approach Data were collected from adult consumers with CCs via an online survey. For model assessment, a two-step approach was followed. First, a measurement model was created and tested using maximum likelihood estimation and validity of the study constructs was assessed. This was followed by structural equation modelling to test the hypotheses. Findings Materialism influences CC use and increases the propensity for IB (IB), which then precipitates CB habits. Reduction in CC use can decrease both IB and CB. Out of the six hypotheses assessed, only the one linking CC use to CB was not supported, requiring further investigation. Mediation relationships were identified, where CC use and IB act as mediators between materialism and CB. Research limitations/implications The paper captured responses from adult consumers of India. Hence, the findings may not be generalised across geographies and age groups. The study contributes to the debate on the impulsive–CB paradigm by showing that impulsive and CB are not distinct constructs. In fact, the former could lead to the latter. Practical implications CC use in itself need not necessarily lead to CB. The only way CC could cause CB is through IB. Hence, firms must promote responsible buying habits, as there has been an increase in IB, which, if not controlled, could lead to debt trap resulting from CB. The findings of this paper will help both retailers and CC institutions to better understand the spending pattern of consumers. Those will also help the policymakers to chalk out ways to the curb indiscriminate issuance of CCs without educating users. Originality/value The findings confirm that IB and CB exist on two ends of a continuum, and not as two distinct theoretical constructs. IB acts as a mediator between CC use and CB as well as between materialism and CB.

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