scholarly journals Nevirapine Exposure with WHO Pediatric Weight Band Dosing: Enhanced Therapeutic Concentrations Predicted Based on Extensive International Pharmacokinetic Experience

2012 ◽  
Vol 56 (10) ◽  
pp. 5374-5380 ◽  
Author(s):  
Mina Nikanjam ◽  
Desiré Kabamba ◽  
Tim R. Cressey ◽  
David Burger ◽  
Francesca T. Aweeka ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pharmacokinetic Model ◽  
Transcriptase Inhibitor ◽  
World Health ◽  
Fixed Dose ◽  
Target Range ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data ◽  
Resource Limited Settings ◽  
Resource Limited

ABSTRACTNevirapine (NVP) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) used worldwide as part of combination antiretroviral therapy in infants and children to treat HIV infection. Dosing based on either weight or body surface area has been approved by the U.S. Food and Drug Administration (FDA) but can be difficult to implement in resource-limited settings. The World Health Organization (WHO) has developed simplified weight band dosing for NVP, but it has not been critically evaluated. NVP pharmacokinetic data were combined from eight pediatric clinical trials (Pediatric AIDS Clinical Trials Group [PACTG] studies 245, 356, 366, 377, 403, 1056, and 1069 and Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens [CHAPAS]) representing subjects from multiple continents and across the pediatric age continuum. A population pharmacokinetic model was developed to characterize developmental changes in NVP disposition, identify potential sources of NVP pharmacokinetic variability, and assess various pediatric dosing strategies and their impact on NVP exposure. Age, CYP2B6 genotype, and ritonavir were independent predictors of oral NVP clearance. The Triomune fixed-dose tablet was an independent predictor of bioavailability compared to the liquid and other tablet formulations. Monte Carlo simulations of the final model were used to assess WHO weight band dosing recommendations. The final pharmacokinetic model indicated that WHO weight band dosing is likely to result in a percentage of children with NVP exposure within the target range similar to that obtained with FDA dosing. Weight band dosing of NVP proposed by the WHO has the potential to provide a simple and effective dosing strategy for resource limited settings.

scholarly journals Simplified Dosing Regimens for Gentamicin in Neonatal Sepsis

2021 ◽  
Vol 12 ◽  
Author(s):  
S. D’Agate ◽  
F. Tshinanu Musuamba ◽  
E. Jacqz-Aigrain ◽  
O. Della Pasqua
Keyword(s):  
Body Weight ◽  
Bacterial Infections ◽  
Drug Disposition ◽  
External Validation ◽  
World Health ◽  
Fixed Dose ◽  
Therapeutic Drug ◽  
Resource Limited Settings ◽  
Young Infants ◽  
Resource Limited

Background: The effectiveness of antibiotics for the treatment of severe bacterial infections in newborns in resource-limited settings has been determined by empirical evidence. However, such an approach does not warrant optimal exposure to antibiotic agents, which are known to show different disposition characteristics in this population. Here we evaluate the rationale for a simplified regimen of gentamicin taking into account the effect of body size and organ maturation on pharmacokinetics. The analysis is supported by efficacy data from a series of clinical trials in this population.Methods: A previously published pharmacokinetic model was used to simulate gentamicin concentration vs. time profiles in a virtual cohort of neonates. Model predictive performance was assessed by supplementary external validation procedures using therapeutic drug monitoring data collected in neonates and young infants with or without sepsis. Subsequently, clinical trial simulations were performed to characterize the exposure to intra-muscular gentamicin after a q.d. regimen. The selection of a simplified regimen was based on peak and trough drug levels during the course of treatment.Results: In contrast to current World Health Organization guidelines, which recommend gentamicin doses between 5 and 7.5 mg/kg, our analysis shows that gentamicin can be used as a fixed dose regimen according to three weight-bands: 10 mg for patients with body weight <2.5 kg, 16 mg for patients with body weight between 2.5 and 4 kg, and 30 mg for those with body weight >4 kg.Conclusion: The choice of the dose of an antibiotic must be supported by a strong scientific rationale, taking into account the differences in drug disposition in the target patient population. Our analysis reveals that a simplified regimen is feasible and could be used in resource-limited settings for the treatment of sepsis in neonates and young infants with sepsis aged 0–59 days.

scholarly journals A Scoping Review Protocol for Supply Chain Management Systems for Point of Care Diagnostics Services: Optimising COVID-19 Testing Capacity in Resource-limited Settings

2021 ◽  
Author(s):  
Kuhlula Maluleke ◽  
Thobeka Dlangalala ◽  
Alfred Musekiwa ◽  
Kabelo Kgarosi ◽  
Sphamandla Nkambule ◽  
...  
Keyword(s):  
Supply Chain ◽  
Supply Chain Management ◽  
Scoping Review ◽  
Point Of Care ◽  
Scientific Journal ◽  
World Health ◽  
Future Research ◽  
Resource Limited Settings ◽  
Chain Management ◽  
Resource Limited

Abstract BackgroundRapid and specific diagnostic tests are essential for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) testing to allow prompt isolation and early treatment initiation if necessary. Currently, reverse transcription polymerase chain reaction (RT-PCR) tests are the gold standard for SARS-CoV-2 testing but are difficult to implement in resource-limited settings with poor access to laboratory infrastructure. Point of care (POC) testing may be more feasible in resource-limited settings because POC testing is cost-effective, easy to perform, results are rapid, and they can be performed at all levels of healthcare by health professionals with minimal training. To ensure equitable access, it is important that SARS-CoV-2 testing is optimised through well-established supply chain management (SCM). Here we outline a protocol for a scoping review aimed at mapping literature on SCM for POC testing in resource limited settings to guide both future research and the implementation of SARS-CoV-2 POC diagnostics. MethodologyThis scoping review will be guided by an adapted version of the Arksey and O’Malley methodological framework. We will search the Medline Ovid, Medline EBSCO, Scopus, PubMed, PsychInfo, Web of Science and EBSCOHost databases. We will search gray literature in the form of dissertations/theses, conference proceedings, websites of international organisations such as the World Health Organisation and government reports. We will include articles reporting evidence published since inception. Language restrictions will not be applied. We will use a search summary table to test the effectiveness of the search strategy. Two reviewers will screen eligible studies using a tool developed for this scoping review. The quality of the included studies will be appraised using the mixed method appraisal tool (MMAT) version 2018. Discussion The proposed scoping review will gather relevant studies on SCM systems for POC diagnostics services globally. We anticipate that this review’s findings will guide future research on SCM systems for POC diagnostics services in resource-limited settings. The results will be published in a scientific journal, presented at relevant conferences and form part of workshops with key stakeholders involved in SCM systems for POC diagnostics services.

scholarly journals A Randomized Comparison of Anthropomorphic Changes With Preferred and Alternative Efavirenz-Based Antiretroviral Regimens in Diverse Multinational Settings

2015 ◽  
Vol 2 (3) ◽  
Author(s):  
Kristine M. Erlandson ◽  
Sineenart Taejaroenkul ◽  
Laura Smeaton ◽  
Amita Gupta ◽  
Isaac L. Singini ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Repeated Measurements ◽  
Resource Limited Settings ◽  
Thigh Circumference ◽  
Cross Sectional ◽  
Mixed Effect ◽  
Randomized Evaluation ◽  
Resource Limited ◽  
Clinical Diagnoses

Abstract Background.  Existing data on anthropomorphic changes in resource-limited settings primarily come from observational or cross-sectional studies. Data from randomized clinical trials are needed to inform treatment decisions in these areas of the world. Methods.  The AIDS Clinical Trials Group Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) study was a prospective, randomized evaluation of the efficacy of emtricitabine/tenofovir + efavirenz (FTC/TDF + EFV) vs lamivudine/zidovudine + efavirenz (3TC/ZDV + EFV) for the initial treatment of human immunodeficiency virus (HIV)-1-infected individuals from resource-diverse settings. Changes in anthropomorphic measures were analyzed using mixed-effect models for repeated measurements, using all available measurements at weeks 48, 96, and 144. Intent-to-treat results are presented; as-treated results were similar. Results.  Five hundred twenty-six participants were randomized to FTC/TDF + EFV, and 519 participants were randomized to 3TC/ZDV + EFV. Significantly greater increases from baseline to week 144 were seen among those randomized to FTC/TDF + EFV vs 3TC/ZDV + EFV in all measures except waist-to-hip ratio, with the following mean changes: weight, 4.8 vs 3.0 kg; body mass index, 1.8 vs 1.1 kg/m2; mid-arm, 1.7 vs 0.7 cm; waist, 5.2 vs 4.3 cm; hip, 3.8 vs 1.4 cm; and mid-thigh circumference, 3.1 vs 0.9 cm. There were 7 clinical diagnoses of lipoatrophy in the 3TC/ZDV + EFV arm compared with none in the FTC/TDF + EFV arm. The proportion of overweight or obese participants increased from 25% (week 0) to 42% (week 144) for FTC/TDF + EFV and from 26% to 38% for 3TC/ZDV + EFV. Conclusions.  Our findings support first-line use of FTC/TDF + EFV in resource-limited settings and emphasize the need for interventions to limit weight gain among overweight or obese HIV-infected participants in all settings.

scholarly journals Characteristics of a Nationwide Voluntary Antibiotic Resistance Awareness Campaign in India; Future Paths and Pointers for Resource Limited Settings/Low and Middle Income Countries

2019 ◽  
Vol 16 (24) ◽  
pp. 5141
Author(s):  
Ashok J. Tamhankar ◽  
Ramesh Nachimuthu ◽  
Ravikant Singh ◽  
Jyoti Harindran ◽  
Gautam Kumar Meghwanshi ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Antibiotic Use ◽  
World Health ◽  
Awareness Campaign ◽  
Resource Limited Settings ◽  
Middle Income ◽  
Middle Income Countries ◽  
Awareness Campaigns ◽  
Resource Limited ◽  
Low And Middle Income

Antibiotic resistance has reached alarming proportions globally, prompting the World Health Organization to advise nations to take up antibiotic awareness campaigns. Several campaigns have been taken up worldwide, mostly by governments. The government of India asked manufacturers to append a ‘redline’ to packages of antibiotics as identification marks and conducted a campaign to inform the general public about it and appropriate antibiotic use. We investigated whether an antibiotic resistance awareness campaign could be organized voluntarily in India and determined the characteristics of the voluntarily organized campaign by administering a questionnaire to the coordinators, who participated in organizing the voluntary campaign India. The campaign characteristics were: multiple electro–physical pedagogical and participatory techniques were used, 49 physical events were organized in various parts of India that included lectures, posters, booklet/pamphlet distribution, audio and video messages, competitions, and mass contact rallies along with broadcast of messages in 11 local languages using community radio stations (CRS) spread all over India. The median values for campaign events were: expenditure—3000 Indian Rupees/day (US$~47), time for planning—1 day, program spread—4 days, program time—4 h, direct and indirect reach of the message—respectively 250 and 500 persons/event. A 2 min play entitled ‘Take antibiotics as prescribed by the doctor’ was broadcast 10 times/day for 5 days on CRS with listener reach of ~5 million persons. More than 85%ofcoordinators thought that the campaign created adequate awareness about appropriate antibiotic use and antibiotic resistance. The voluntary campaign has implications for resource limited settings/low and middle income countries.

scholarly journals Population Pharmacokinetics and Dosing Optimization of Linezolid in Pediatric Patients

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Si-Chan Li ◽  
Qi Ye ◽  
Hua Xu ◽  
Long Zhang ◽  
Yang Wang
Keyword(s):  
Body Weight ◽  
Population Pharmacokinetics ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Pediatric Patients ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data ◽  
Nonparametric Bootstrap ◽  
Bootstrap Analysis ◽  
Final Model

ABSTRACT Linezolid is a synthetic antibiotic very effective in the treatment of infections caused by Gram-positive pathogens. Although the clinical application of linezolid in children has increased progressively, data on linezolid pharmacokinetics in pediatric patients are very limited. The aim of this study was to develop a population pharmacokinetic model for linezolid in children and optimize the dosing strategy in order to improve therapeutic efficacy. We performed a prospective pharmacokinetic study of pediatric patients aged 0 to 12 years. The population pharmacokinetic model was developed using the NONMEM program. Goodness-of-fit plots, nonparametric bootstrap analysis, normalized prediction distribution errors, and a visual predictive check were employed to evaluate the final model. The dosing regimen was optimized based on the final model. The pharmacokinetic data from 112 pediatric patients ages 0.03 to 11.9 years were analyzed. The pharmacokinetics could best be described by a one-compartment model with first-order elimination along with body weight and the estimated glomerular filtration rate as significant covariates. Simulations demonstrated that the currently approved dosage of 10 mg/kg of body weight every 8 h (q8h) would lead to a high risk of underdosing for children in the presence of bacteria with MICs of ≥2 mg/liter. To reach the pharmacokinetic target, an elevated dosage of 15 or 20 mg/kg q8h may be required for them. The population pharmacokinetics of linezolid were characterized in pediatric patients, and simulations provide an evidence-based approach for linezolid dosage individualization.

Exploratory analysis of population pharmacokinetic data from clinical trials with application to isradipine

1991 ◽  
Vol 50 (1) ◽  
pp. 39-54 ◽  
Author(s):  
Robert Laplanche ◽  
Bernard Fertil ◽  
Erich Nüesch ◽  
Jean-Philippe Jais ◽  
Werner Niederberger ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Exploratory Analysis ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data

scholarly journals EDITORIAL: COVID-19: Rebooting pharmacy education in resource-limited settings

2021 ◽  
pp. 67-70
Author(s):  
Jennie Lates ◽  
Dan Kibuule
Keyword(s):  
Health Systems ◽  
World Health Organisation ◽  
Pharmacy Education ◽  
Sub Saharan Africa ◽  
World Health ◽  
Resource Limited Settings ◽  
Non Communicable Diseases ◽  
High Burden ◽  
Resource Limited ◽  
Sub Saharan

Globally, the COVID-19 pandemic has aggravated inequalities in access to quality pharmacy education, particularly in resource-limited settings in Africa (Engle, 2020; Fuller et al., 2020). This is a serious concern for Africa especially, given that sub-Saharan Africa ranks lowest on the global pharmaceutical workforce index and has a disproportionately high burden of infectious and non-communicable diseases, combined with weak health systems (World Health Organisation [WHO], 2013; Bates et al., 2018).

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