scholarly journals Population Pharmacokinetic Properties of Sulfadoxine and Pyrimethamine: a Pooled Analysis To Inform Optimal Dosing in African Children with Uncomplicated Malaria

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Miné de Kock ◽  
Joel Tarning ◽  
Lesley Workman ◽  
Elizabeth N. Allen ◽  
Mamadou M. Tekete ◽  
...  
Keyword(s):  
Body Weight ◽  
Young Children ◽  
Total Body Weight ◽  
Pooled Analysis ◽  
World Health ◽  
Population Pharmacokinetic ◽  
Z Score ◽  
Dosing Regimen ◽  
Optimal Dosing ◽  
Health Organization

ABSTRACT Sulfadoxine-pyrimethamine with amodiaquine is recommended by the World Health Organization as seasonal malaria chemoprevention for children aged 3 to 59 months in the sub-Sahel regions of Africa. Suboptimal dosing in children may lead to treatment failure and increased resistance. Pooled individual patient data from four previously published trials on the pharmacokinetics of sulfadoxine and pyrimethamine in 415 pediatric and 386 adult patients were analyzed using nonlinear mixed-effects modeling to evaluate the current dosing regimen and, if needed, to propose an optimized dosing regimen for children under 5 years of age. The population pharmacokinetics of sulfadoxine and pyrimethamine were both best described by a one-compartment disposition model with first-order absorption and elimination. Body weight, age, and nutritional status (measured as the weight-for-age Z-score) were found to be significant covariates. Allometric scaling with total body weight and the maturation of clearance in children by postgestational age improved the model fit. Underweight-for-age children were found to have 15.3% and 26.7% lower bioavailabilities of sulfadoxine and pyrimethamine, respectively, for each Z-score unit below −2. Under current dosing recommendations, simulation predicted that the median day 7 concentration was below the 25th percentile for a typical adult patient (50 kg) for sulfadoxine for patients in the weight bands of 8 to 9, 19 to 24, 46 to 49, and 74 to 79 kg and for pyrimethamine for patients in the weight bands of 8 to 9, 14 to 24, and 42 to 49 kg. An evidence-based dosing regimen was constructed that would achieve sulfadoxine and pyrimethamine exposures in young children and underweight-for-age young children that were similar to those currently seen in a typical adult.

scholarly journals Model-oriented Dose Optimization of Voriconazole in Critically Ill Children

2021 ◽  
Author(s):  
Jun Wang ◽  
Hua Xu ◽  
Ran Li ◽  
Sanlan Wu ◽  
Jili Zou ◽  
...  
Keyword(s):  
Body Weight ◽  
Critically Ill ◽  
Maintenance Dose ◽  
Maximum Velocity ◽  
Critically Ill Children ◽  
Population Pharmacokinetic ◽  
Dosing Regimen ◽  
Final Model ◽  
Optimal Dosing ◽  
Dosing Regimens

Objective: This study aimed to employ a population pharmacokinetic (PK) model to optimize the dosing regimen of voriconazole (VRC) in children with a critical illness. Methods: A total of 99 children aged from 0.44 to 13.58 years old were included in this study. The stability and predictive performance of the final model were evaluated by statistical and graphical methods. The optimal dosing regimen was proposed for children with different body weight, CYP2C19 phenotype, and co-administration with omeprazole. Results: The PK of VRC was described by a two-compartment model with nonlinear Michaelis-Menten elimination. Body weight, CYP2C19 phenotype, and omeprazole were significant covariates on maximum velocity of elimination (V max ), which had an estimated typical value of 18.13 mg·h −1 . Bayesian estimation suggested that dose-normalized concentration and total exposure (C max /D, C min /D, AUC 24 /D) were significantly different between extensive metabolizers (EM) patients and poor metabolizer (PM) patients. To achieve the target concentration early, two loading doses of 9 mg·kg −1 q12h were reliable for most children, whereas three loading doses of 6-7.5 mg·kg −1 q8h were warranted for young children weighted ≤18kg (except PM patients). The maintenance doses decreased about 30-40% in PM patients than that in EM patients. For children aged < 2 years in EM, the maintenance dose could be as high as 9 mg·kg −1 . The maintenance dose of VRC was supposed to decrease slightly when co-administration with omeprazole. Conclusion: A population PK model of intravenous VRC for critically ill children has been successful developed. It is necessary to adjust dosing regimens according to CYP2C19 genotype. The optimal dosing regimens have been recommended basing on the final model.

scholarly journals Optimal Household Water Access Fosters the Attainment of Minimum Dietary Diversity among Children Aged 6–23 Months in Malawi

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 178
Author(s):  
Zizwani Brian Chilinda ◽  
Mark L. Wahlqvist ◽  
Meei-Shyuan Lee ◽  
Yi-Chen Huang
Keyword(s):  
Young Children ◽  
Dietary Diversity ◽  
World Health ◽  
Food Groups ◽  
Water Access ◽  
Direct Role ◽  
Cross Sectional ◽  
Child Undernutrition ◽  
Health Organization ◽  
Minimum Dietary Diversity

Along with sanitation and hygiene, water is a well-known driver of child undernutrition. However, a more direct role of household (HH) water access in shaping dietary diversity remains unexplored. We assessed the association between HH water access and achievement of minimum dietary diversity (MDD) among young children. We utilized nationally-representative cross-sectional data from the 2015/16 Malawi Demographic and Health Survey, which included 4727 mother–child dyads, respectively, (26.8 ± 6.8 years, range 15–49 years) and (13.9 ± 4.9 months, range 6–23 months). HH water access was categorized as (1) basic or no access, (2) intermediate, or (3) optimal. MDD was defined as feeding a child, during the previous day, at least four of the food groups defined by the World Health Organization. Only 27.7% of the children achieved MDD standards; most of the children who achieved MDD were from HHs with optimal water access (58.4%, p < 0.001). However, only 5.9% of the mother–child dyads were from HHs with optimal water access. After adjusting for covariates, children from HHs with optimal water access had higher odds of achieving MDD than those from HHs with basic or no water access (aOR = 1.74, CI = 1.24–2.46). Our results highlight the need to incorporate water-based strategies into national nutritional policies to increase dietary diversity among Malawian infants and young children.

scholarly journals Multicenter Population Pharmacokinetic Study of Colistimethate Sodium and Colistin Dosed as in Normal Renal Function in Patients on Continuous Renal Replacement Therapy

2018 ◽  
Vol 63 (2) ◽  
pp. e01957-18 ◽  
Author(s):  
Anne B. Leuppi-Taegtmeyer ◽  
Laurent Decosterd ◽  
Michael Osthoff ◽  
Nicolas J. Mueller ◽  
Thierry Buclin ◽  
...  
Keyword(s):  
Renal Function ◽  
Body Weight ◽  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Normal Renal Function ◽  
Maintenance Dose ◽  
Population Pharmacokinetic ◽  
Loading Dose ◽  
Optimal Dosing ◽  
Colistimethate Sodium

ABSTRACT Intravenous colistimethate sodium (CMS) is used to treat infections with multiresistant Gram-negative bacteria. Optimal dosing in patients undergoing continuous renal replacement therapy (CRRT) is unclear. In a prospective study, we determined CMS and colistin pharmacokinetics in 10 critically ill patients requiring CRRT (8 underwent continuous venovenous hemodialysis [CVVHD]; median blood flow, 100 ml/min). Intensive sampling was performed on treatment days 1, 3, and 5 after an intravenous CMS loading dose of 9 million international units (MU) (6 MU if body weight was <60 kg) with a consecutive 3-MU (respectively, 2 MU) maintenance dose at 8 h. CMS and colistin concentrations were determined by liquid chromatography with mass spectroscopy. A model-based population pharmacokinetic analysis incorporating CRRT settings was applied to the observations. Sequential model building indicated a monocompartmental distribution for both CMS and colistin, with interindividual variability in both volume and clearance. Hematocrit was shown to affect the efficacy of drug transfer across the filter. CRRT clearance accounted for, on average, 41% of total CMS and 28% of total colistin clearance, confirming enhanced elimination of colistin compared to normal renal function. Target colistin steady-state trough concentrations of at least 2.5 mg/liter were achieved in all patients receiving 3 MU at 8 h. In conclusion, a loading dose of 9 MU followed after 8 h by a maintenance dose of 3 MU every 8 h independent of body weight is expected to achieve therapeutic colistin concentrations in patients undergoing CVVHD using low blood flows. Colistin therapeutic drug monitoring might help to further ensure optimal dosing in individual patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02081560.)

scholarly journals Comparative analysis of children’s physical development in different age groups in Voronezh region 15 years apart (1997-1999 and 2011-2014)

2017 ◽  
Vol 98 (3) ◽  
pp. 433-439
Author(s):  
O A Zhdanova
Keyword(s):  
Body Mass Index ◽  
Body Weight ◽  
Body Mass ◽  
Body Height ◽  
Age Groups ◽  
Physical Development ◽  
World Health ◽  
Who Standards ◽  
Voronezh Region ◽  
Health Organization

Aim. To investigate physical development of children in Voronezh region in different age groups in 2011-2014 in comparison with the regional studies data in 1997-1999. Methods. The study was performed on 5644 children aged 1-18 years of health groups I and II in comparison with the data of 10 247 children aged 1-14 years examined in 1997-1999. Body height, weight and body mass index Z-scores, calculated using WHO AnthroPlus software, were evaluated. Results. Children’s Z-score values for body height in 2011-2014 were higher than in 1997-1999 in all age groups and at the age of 1-9 years these values exceeded World Health Organization (WHO) standards. Girls’ height approached the standards in 10-14 and 15-18 years, and boys’ height - in 15-18 years. Body weight of children aged 2-8 years was higher than the regional data in 1997-1999 and WHO standards approaching them at the age of 9. Body mass index increase compared to WHO standards was revealed in children aged 1-4 years (p=0.000), and in 2011-2014 the reported differences were less prominent than in 1997-1999. In 2011-2014 among 15-18-years-old girls the shift of body mass index values to the lack of body weight was noted, in 1997-1999 the same changes were found out for 10-14-years-old girls. Conclusion. In 2011-2014 specific attention was required to be paid to physical development of children at the age from 1 to 4 years due to overweight risk of and girls aged 15-18 years due to probable underweight risk.

scholarly journals HUBUNGAN STUNTING DENGAN KARAKTERISTIK ANAK, ASUPAN GIZI, DAN ANEMIA PADA BATITA DI WILAYAH PUSKESMAS CIBEBER

2021 ◽  
pp. 293-304
Author(s):  
Dinar Mutiara ◽  
Andri Andrian Rusman ◽  
Rizky Sukma Ruhimat
Keyword(s):  
World Health Organization ◽  
World Health ◽  
Z Score ◽  
Probability Sampling ◽  
Consecutive Sampling ◽  
Growth Reference ◽  
Food Recall ◽  
X 24 ◽  
Health Organization

Stunting adalah suatu keadaan tinggi badan menurut umur (TB/U) seseorang yang tidak sesuai dengan umur dan merupakan indikator dari malnutrisi pada anak usia dini. Seseorang dikatakan stunting bila z-score indeks TB/U atau PB/U-nya kurang dari (-2) standar deviasi berdasarkan World Health Organization-Multicentre Growth Reference Study (WHO-MGRS). Tujuan penelitian ini adalah untuk mengetahui hubungan stunting dengan karakteristik anak (usia, jenis kelamin, dan BBLR), asupan zat gizi (asupan zat besi dan protein), dan anemia pada anak batita di wilayah Puskesmas Cibeber. Penelitian ini dilakukan dengan metode analitik secara potong lintang. Pengumpulan sampel diambil dengan cara non-probability sampling, yaitu menggunakan metode consecutive sampling pada bulan Januari - Februari 2021 dan diperoleh 32 sampel. Instrumen yang digunakan berupa alat ukur tinggi badan, hemoglobinometer, dan lembar food recall 2 x 24 jam. Hasil uji statistik kai kuadrat didapatkan adanya hubungan yang signifikan antara asupan zat gizi dengan kejadian stunting pada batita, yaitu asupan protein dengan nilai p= 0,012 dan asupan zat besi dengan nilai p=0,028. Tidak terdapat hubungan yang signifikan pada jenis kelamin dengan nilai p= 0,476, BBLR dengan nilai p= 0,365, dan anemia dengan nilai p= 0,288 dengan kejadian stunting pada anak batita. Kesimpulan pada penelitian ini setelah dilakukan uji bivariat adalah faktor asupan zat gizi yang berupa asupan zat besi dan protein memiliki hubungan yang signifikan dengan kejadian stunting pada anak batita. Pemenuhan kebutuhan gizi batita sangat dibutuhkan untuk mencegah stunting sehingga proses perkembangan anak batita dapat berjalan sesuai dengan tahapannya.

scholarly journals Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants

2019 ◽  
Vol 74 (8) ◽  
pp. 2128-2138 ◽  
Author(s):  
Evelyne Jacqz-Aigrain ◽  
Stéphanie Leroux ◽  
Alison H Thomson ◽  
Karel Allegaert ◽  
Edmund V Capparelli ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Intermittent Infusion ◽  
Compartment Model ◽  
Population Pharmacokinetic ◽  
Dosing Regimen ◽  
Blue Book ◽  
Young Infants ◽  
Optimal Dosing ◽  
Two Compartment Model ◽  
Postmenstrual Age

Abstract Objectives In the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates. Methods A ‘meta-model’ with 4894 concentrations from 1631 neonates was built using NONMEM, and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming to reach a target AUC0–24 of 400 mg·h/L at steady-state in at least 80% of neonates. Results A two-compartment model best fitted the data. Current weight, postmenstrual age (PMA) and serum creatinine were the significant covariates for CL. After model validation, simulations showed that a loading dose (25 mg/kg) and a maintenance dose (15 mg/kg q12h if <35 weeks PMA and 15 mg/kg q8h if ≥35 weeks PMA) achieved the AUC0–24 target earlier than a standard ‘Blue Book’ dosage regimen in >89% of the treated patients. Conclusions The results of a population meta-analysis of vancomycin data have been used to develop a new dosing regimen for neonatal use and to assist in the design of the model-based, multinational European trial, NeoVanc.

scholarly journals Pharmacokinetics of Ceftaroline in Normal Body Weight and Obese (Classes I, II, and III) Healthy Adult Subjects

2015 ◽  
Vol 59 (7) ◽  
pp. 3956-3965 ◽  
Author(s):  
Julie Ann Justo ◽  
Stockton M. Mayer ◽  
Manjunath P. Pai ◽  
Melinda M. Soriano ◽  
Larry H. Danziger ◽  
...  
Keyword(s):  
Body Weight ◽  
Healthy Adult ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Total Body Weight ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Population Pharmacokinetic ◽  
Ceftaroline Fosamil ◽  
Plasma And Urine Samples

ABSTRACTThe pharmacokinetic profile of ceftaroline has not been well characterized in obese adults. The purpose of this study was to evaluate the pharmacokinetics of ceftaroline in 32 healthy adult volunteers aged 18 to 50 years in the normal, overweight, and obese body size ranges. Subjects were evenly assigned to 1 of 4 groups based on their body mass index (BMI) and total body weight (TBW) (ranges, 22.1 to 63.5 kg/m2and 50.1 to 179.5 kg, respectively). Subjects in the lower-TBW groups were matched by age, sex, race/ethnicity, and serum creatinine to the upper-BMI groups. Serial plasma and urine samples were collected over 12 h after the start of the infusion, and the concentrations of ceftaroline fosamil (prodrug), ceftaroline, and ceftaroline M-1 (inactive metabolite) were assayed. Noncompartmental and population pharmacokinetic analyses were used to evaluate the data. The mean plasma ceftaroline maximum concentration and area under the curve were ca. 30% lower in subjects with a BMI of ≥40 kg/m2compared to those <30 kg/m2. A five-compartment pharmacokinetic model with zero-order infusion and first-order elimination optimally described the plasma concentration-time profiles of the prodrug and ceftaroline. Estimated creatinine clearance (eCLCR) and TBW best explained ceftaroline clearance and volume of distribution, respectively. Although lower ceftaroline plasma concentrations were observed in obese subjects, Monte Carlo simulations suggest the probability of target attainment is ≥90% when the MIC is ≤1 μg/ml irrespective of TBW or eCLCR. No dosage adjustment for ceftaroline appears to be necessary based on TBW alone in adults with comparable eCLCR. Confirmation of these findings in infected obese patients is necessary to validate these findings in healthy volunteers. (This study has been registered at ClinicalTrials.gov under registration no. NCT01648127.)

ANALISIS PENGELUARAN PANGAN, KETAHANAN PANGAN DAN ASUPAN ZAT GIZI ANAK BAWAH DUA TAHUN (BADUTA) SEBAGAI FAKTOR RISIKO STUNTING

2020 ◽  
Vol 9 (1) ◽  
pp. 71-80
Author(s):  
Eta Aprita Aritonang ◽  
Ani Margawati ◽  
Fillah Fithra Dieny
Keyword(s):  
Food Security ◽  
Vitamin A ◽  
Case Control ◽  
World Health ◽  
Household Food Security ◽  
Z Score ◽  
Chi Square ◽  
Food Frequency ◽  
Household Food ◽  
Health Organization

Latar Belakang : Beberapa faktor yang mempengaruhi terjadinya stunting anak usia 6-24 bulan antara lain kurangnya asupan zat gizi, penyakit infeksi, lingkungan, sosial ekonomi keluarga dan riwayat kehamilan ibu. Penelitian ini bertujuan menganalisis proporsi pengeluaran pangan rumah tangga, ketahanan pangan, dan asupan zat gizi sebagai faktor risiko terjadinya stunting usia 6-24 bulan.Metode : Penelitian ini menggunakan desain case-control dengan masing-masing kelompok kasus (stunting) dan kontrol (tidak stunting) berjumlah 24 sampel yang diambil menggunakan purposive sampling pada anak usia 6-24 bulan yang berada di Semarang Utara. Stunting diukur berdasarkan z-score tinggi badan menurut umur (TB/U) dianalisis dengan software World Health Organization (WHO) Anthro. Data yang diambil yaitu berat badan lahir, panjang badan lahir, tingkat pendidikan ibu, pendapatan keluarga dan pengeluaran rumah tangga. Data riwayat asupan energi, protein, vitamin A dan seng selama 1 tahun diperoleh dengan menggunakan Semi Quantitative Food Frequency Questionnaire (SQ-FFQ). Data ketahanan pangan diperoleh dengan menggunakan kuisioner Household Food Security Scale Module (HFSSM). Data dianalisis dengan menggunakan uji Chi Square dan analisis regresi logistik.Hasil : Baduta stunting lebih banyak mengalami kerawanan pangan rumah tangga (79,2%), riwayat kekurangan asupan protein (70,8%), vitamin A (75%) dan seng (66,7%) dibandingkan dengan anak yang tidak stunting. Ketahanan pangan rumah tangga (OR=6,9), riwayat asupan protein (OR=8,6), vitamin A (OR=20,6) dan seng (OR=8,7) merupakan faktor yang paling berisiko terhadap kejadian stunting pada baduta usia 6-24 bulan (p<0,05).Simpulan: Kerawanan pangan rumah tangga, kurangnya asupan protein, vitamin A dan seng merupakan faktor yang berisiko meningkatkan kejadian stunting pada baduta usia 6-24 bulan.

scholarly journals Trends in child growth failure among children under five years of age in Ethiopia: Evidence from the 2000 to 2016 Demographic and Health Surveys

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0254768
Author(s):  
Tolesa Bekele ◽  
Patrick Rawstorne ◽  
Bayzidur Rahman
Keyword(s):  
Growth Failure ◽  
Total Sample ◽  
Child Growth ◽  
World Health ◽  
Health Concern ◽  
Demographic And Health Surveys ◽  
Z Score ◽  
Middle Income ◽  
The Government ◽  
Health Organization

Introduction In a majority of low- and middle-income countries (LMICs), levels of child growth failure (CGF) have steadily declined since 2000. However, some countries show a different trend. Despite continued investment from the government of Ethiopia as well as donors, CGF levels are still high in Ethiopia. This study aimed to assess trends in CGF and associated sociodemographic, economic and water, sanitation, and hygiene (WASH) factors from 2000 to 2016 in Ethiopia. Methods Data were taken from four rounds of the Ethiopia Demographic and Health Survey (EDHS). Children aged between 0 to 59 months were included. CGF indicators were categorised based on height-for-age z-score (HAZ) < -2 Standard deviation (SD), weight-for-age z-score (WAZ) < -2 SD and weight-for-height z-score (WHZ) < -2 SD. CGF trends were estimated for predicted probabilities and odds ratios (ORs) between 2000 and 2016. Results A total sample size of 31978 for HAZ, 32045 for WAZ and 32246 for WHZ were included in the current study. Stunting decreased from an adjusted odds ratio (AOR) = 0.77 (95% CI: 0.67 to 0.88) in 2005 to an AOR = 0.45 (95% CI: 0.39 to 0.53) in 2016 compared with the year 2000. Compared with data in 2000, underweight decreased from an AOR of 0.70 (95% CI: 0.61 to 0.80) in 2005 to an AOR of 0.43 (95% CI: 0.36 to 0.50) in 2016. Wasting declined from an AOR of 0.91 (95% CI: 0.75 to 1.10) in 2005 to an AOR of 0.76 (95% CI: 0.61 to 0.94) in 2016, compared with data in 2000. Conclusions Between 2000 to 2016, there was a decline in CGF levels albeit the levels are still relatively high compared with the World Health Organization (WHO) cut-off levels for public health concern. Observed rates of change varied across sociodemographic, economic and WASH factors which suggest that interventions tailored towards addressing the imbalances across those factors are required.

scholarly journals Anti-malaria and hypoglycaemic activities of Diosgenin on alloxan-induced, diabetic Wistar rats

2021 ◽  
Vol 15 (3) ◽  
pp. 073-079
Author(s):  
Omoirri Moses Aziakpono ◽  
Madubogwu Ngozi Ukamaka ◽  
Oraekei Daniel Ikechukwu ◽  
Ataihire Johnson Uyovwiesevwa ◽  
Chukwuemeka Charles Ofili ◽  
...  
Keyword(s):  
Body Weight ◽  
Blood Sugar ◽  
Wistar Rats ◽  
World Health ◽  
Treatment Groups ◽  
Male Wistar Rats ◽  
Normal Rat ◽  
Sugar Levels ◽  
Health Organization ◽  
Alloxan Monohydrate

The rising threat of Plasmodium falciparum resistance to Monotherapies has prompted the world health organization (WHO) 2006 guidelines to recommend the use of different anti-malarias. In this study, the anti-malaria and hypoglycaemic activities of Diosgenin, a potent, yet poorly reported saponin was investigated on P. falciparum inoculated and Alloxan-Induced, Diabetic Wistar Rats. Fort two (42) adult male wistar rats of between 100g and 150g were procured, acclimatized (for two weeks), and grouped into seven of six (6) rats per group. While Group 1 (Normal control) received normal rat chow and water ad libitum, groups 2 – 4 received no treatment (untreated), 10 mg/kg body weight of anti-diabetic Metformin and 25 mg/kg body weight of diosgenin respectively after inducing diabetes mellitus (DM) with alloxan monohydrate; whereas, groups 5-7 (all malaria infected) were untreated (negative malaria control), 25 mg/kg body weight of diosgenin and 56 mg/kg body weight of anti-malaria coartem respectively. Following treatment period, blood samples were obtained and assayed for fasting blood sugar, packed cell volume (PCV) and total white blood cell count (TWBCC). From the result, P. falciparum exposed rats showed lowered PCV values than control with observed improvements in coartem (significant at p < 0.05) and diosgenin (insignificant) treatment groups. Also, diabetic, diosgenin treated rats showed an insignificant reduction in blood sugar levels compared to control, even though this change was apparently improved compared to diabetic, untreated group. Again, TWBCC caused notable decrease in diosgenin treated, though this decrease signified a huge recovery compared to untreated rats. Corroborative studies on diosgenin with other systems is recommended.

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