scholarly journals Population Pharmacokinetics of Intramuscular Artesunate in African Children With Severe Malaria: Implications for a Practical Dosing Regimen

2013 ◽  
Vol 93 (5) ◽  
pp. 443-450 ◽  
Author(s):  
ICE Hendriksen ◽  
G Mtove ◽  
A Kent ◽  
S Gesase ◽  
H Reyburn ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Severe Malaria ◽  
Dosing Regimen ◽  
African Children ◽  
Intramuscular Artesunate

scholarly journals Intramuscular Artesunate for Severe Malaria in African Children: A Multicenter Randomized Controlled Trial

PLoS Medicine ◽  
2016 ◽  
Vol 13 (1) ◽  
pp. e1001938 ◽  
Author(s):  
Peter G. Kremsner ◽  
Akim A. Adegnika ◽  
Aurore B. Hounkpatin ◽  
Jeannot F. Zinsou ◽  
Terrie E. Taylor ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Severe Malaria ◽  
Controlled Trial ◽  
Randomized Controlled ◽  
African Children ◽  
Multicenter Randomized Controlled Trial ◽  
Intramuscular Artesunate

POPULATION PHARMACOKINETICS AND DOSING OPTIMIZATION OF TEICOPLANIN IN CHILDREN WITH MALIGNANT HAEMATOLOGICAL DISEASE

2015 ◽  
Vol 101 (1) ◽  
pp. e1.41-e1
Author(s):  
Wei Zhao ◽  
Daolun Zhang ◽  
Thomas Storme ◽  
André Baruchel ◽  
Xavier Declèves ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Haematological Malignancy ◽  
External Validation ◽  
Predictive Performance ◽  
Paediatric Population ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
High Risk Population ◽  
Dosing Regimen

BackgroundChildren with haematological malignancy represent an identified subgroup of the paediatric population with specific pharmacokinetic parameters. In these patients, inadequate empirical antibacterial therapy may result in infection-related morbidity and increased mortality, making optimization of the dosing regimen essential. As paediatric data are limited, our aim was to evaluate the population pharmacokinetics of teicoplanin in order to define the appropriate dosing regimen in this high-risk population.MethodsThe current dose of teicoplanin was evaluated in children with haematological malignancy. Population pharmacokinetics of teicoplanin was analysed using NONMEM software. The dosing regimen was optimised based on the final model.ResultsEighty-five children (age range: 0.5 to 16.9 years) were included. Therapeutic drug monitoring and opportunistic samples (n=143) were available for analysis. With the current recommended dose of 10 mg/kg/day, 41 children (48%) had sub-therapeutic steady-state trough concentrations (Css,min<10 mg/liter). A two-compartment pharmacokinetic model with first-order elimination was developed. Systematic covariate analysis identified that bodyweight (size) and creatinine clearance significantly influenced teicoplanin clearance. The model was validated internally. Its predictive performance was further confirmed in an external validation. In order to reach the target AUC of 750 mg·h/L, 18 mg/kg was required for infants, 14 mg/kg for children and 12 mg/kg for adolescents. A patient-tailored dose regimen was further developed and reduced variability in AUC and Css,min values compared to the mg/kg-basis dose, making the modelling approach an important tool for dosing individualization.ConclusionsThis first population pharmacokinetic study of teicoplanin in children with haematological malignancy provided evidence-based support to individualize teicoplanin therapy in this vulnerable population.

scholarly journals Molecular markers of anti-malarial drug resistance in Central, West and East African children with severe malaria

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Christian N. Nguetse ◽  
Ayola Akim Adegnika ◽  
Tsiri Agbenyega ◽  
Bernhards R. Ogutu ◽  
Sanjeev Krishna ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Molecular Markers ◽  
Severe Malaria ◽  
East African ◽  
African Children

Identifying targets of protective antibodies against severe malaria in Papua, Indonesia using locally expressed domains of Plasmodium falciparum Erythrocyte Membrane Protein 1.

2021 ◽  
Author(s):  
Janavi S Rambhatla ◽  
Gerry Q Tonkin-Hill ◽  
Eizo Takashima ◽  
Takafumi Tsuboi ◽  
Rintis Noviyanti ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Severe Malaria ◽  
Erythrocyte Membrane ◽  
Uncomplicated Malaria ◽  
Igg Antibodies ◽  
Erythrocyte Membrane Protein ◽  
African Children ◽  
Genes Encoding ◽  
Malaria Severity

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a diverse family of multi-domain proteins expressed on the surface of malaria-infected erythrocytes, is an important target of protective immunity against malaria. Our group recently studied transcription of the var genes encoding PfEMP1 in individuals from Papua, Indonesia with severe or uncomplicated malaria. We cloned and expressed domains from 32 PfEMP1s including 22 that were upregulated in severe malaria and 10 that were upregulated in uncomplicated malaria, using a wheat germ cell-free expression system. We used Luminex technology to measure IgG antibodies to these 32 domains and control proteins in 63 individuals (11 children). At presentation to hospital, levels of antibodies to PfEMP1 domains were either higher in uncomplicated malaria or were not significantly different between groups. Using principal components analysis, antibodies to three of 32 domains were highly discriminatory between groups. These included two domains upregulated in severe malaria, a DBLβ13 domain and a CIDRα1.6 domain (which has been previously implicated in severe malaria pathogenesis), and a DBLδ domain that was upregulated in uncomplicated malaria. Antibody to control non-PfEMP1 antigens did not differ with disease severity. Antibodies to PfEMP1 domains differ with malaria severity. Lack of antibodies to locally expressed PfEMP1 types, including both domains previously associated with severe malaria and newly identified targets, may in part explain malaria severity in Papuan adults. Importance Severe Plasmodium falciparum malaria kills many African children, and lack of antibody immunity predisposes to severe disease. A critical antibody target is the P. falciparum erythrocyte membrane 1 (PfEMP1) family of multidomain proteins, which are expressed on the infected erythrocyte surface and mediate parasite sequestration in deep organs. We previously identified var genes encoding PfEMP1 that were differentially expressed between severe and uncomplicated malaria in Papua, Indonesia. Here, we have expressed domains from 32 of these PfEMP1s and measured IgG antibody responses to them in Papuan adults and children. Using Principal Component Analysis, IgG antibodies to three domains distinguished between severe and uncomplicated malaria and were higher in uncomplicated malaria. Domains included CIDRα1.6, implicated in severe malaria; a DBLβ13 domain; and a DBLδ domain of unknown function. Immunity to locally relevant PfEMP1 domains may protect from severe malaria. Targets of immunity show important overlap between Asian adults and African children.

scholarly journals Mortality Patterns and Site Heterogeneity of Severe Malaria in African Children

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e58686 ◽  
Author(s):  
Eric Kendjo ◽  
Tsiri Agbenyega ◽  
Kalifa Bojang ◽  
Charles R. J. C. Newton ◽  
Marielle Bouyou-Akotet ◽  
...  
Keyword(s):  
Severe Malaria ◽  
African Children ◽  
Site Heterogeneity

scholarly journals Population Pharmacokinetics and Dosing Optimization of Azithromycin in Children with Community-Acquired Pneumonia

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Yi Zheng ◽  
Shu-Ping Liu ◽  
Bao-Ping Xu ◽  
Zhong-Ren Shi ◽  
Kai Wang ◽  
...  
Keyword(s):  
Body Weight ◽  
Population Pharmacokinetics ◽  
Pediatric Patients ◽  
Community Acquired Pneumonia ◽  
Pharmacodynamic Modeling ◽  
Pharmacokinetic Data ◽  
Loading Dose ◽  
Dosing Regimen ◽  
Time Curve ◽  
Dose Strategy

ABSTRACT Azithromycin is extensively used in children with community-acquired pneumonia (CAP). Currently, the intravenous azithromycin is used off-label in children partly due to lacking of pharmacokinetic data. Our objective was to evaluate the population pharmacokinetics (PPK) and optimize dose strategy in order to improve treatment in this distinctive population. This was a prospective, multicenter, open-labeled pharmacokinetic study. Blood samples were collected from hospitalized pediatric patients and concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). PPK analysis was conducted using NONMEM software. The pharmacokinetic data from 95 pediatric patients (age range, 2.1 to 11.7 years) were available for analysis. The PPK was best fitted by a two-compartment model with linear elimination. Covariate analysis verified that body weight and alanine aminotransferase (ALT) had significant effects on azithromycin pharmacokinetics, yielding a 24% decrease of clearance in patients with ALT of >40. Monte Carlo simulation showed that for children with normal liver function, a loading-dose strategy (a loading dose of 15 mg/kg of body weight followed by maintenance doses of 10 mg/kg) would achieve the ratio of the area under free drug plasma concentration-time curve over 24 h (fAUC) to MIC90 (fAUC/MIC) target of 3 h in 53.2% of hypothetical patients, using a normative MIC susceptibility breakpoint of 2 mg/liter. For children with ALT of >40, the proposed dose needed to decrease by 15% to achieve comparable exposure. The corresponding risk of overdose for the recommended dosing regimen was less than 5.8%. In conclusion, the PPK of azithromycin was evaluated in children with CAP and an optimal dosing regimen was constructed based on developmental pharmacokinetic-pharmacodynamic modeling and simulation.

Severe Malaria in African Children

2018 ◽  
Vol 19 (3) ◽  
pp. 262-263
Author(s):  
Shreya Moodley ◽  
Niranjan Kissoon
Keyword(s):  
Severe Malaria ◽  
African Children
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