Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Int J Pharm ; 655: 123993, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38484862

RESUMO

Amoxicillin, doxycycline, and clindamycin are among the commonly used antibiotics to treat bacterial infections. However, dosage forms of antibiotics for pediatric patients may not be as readily available as the formulations for adult patients. As such, it is anticipated that during a public health emergency, special instruction may need to be provided on home preparation and administration procedures to dose pediatric patients using available stockpiles of oral tablet and capsule dosage forms. Mixing crushed tablets or capsule contents with soft- or liquid- foods is one of the most common home preparation procedures. To gain knowledge for safe and effective use of prepared drug product instead of the intended intact dosage form, the impact of manipulation of the dosage form was studied. Capsule opening, capsule content assay and uniformity, dissolution, homogeneity, and stability studies of drug mixed with various liquid and soft foods were carried out using intact capsules of amoxicillin, doxycycline, and clindamycin. Higher recovery of capsule contents was achieved when using hands or knives to open capsules compared to using scissors. The capsules of all three antibiotic products contained the labeled amount of active pharmaceutical ingredients (API). The peanut butter-drug mixtures failed both United States Pharmacopeia (USP) assay and dissolution criteria because the peanut butter significantly affected the solubility of the drugs, and hence it was omitted from further study. All drug-food mixtures of the three antibiotic products and 15 selected foods exhibited fast dissolution (e.g., >80 % in 60 min) in the tested medium, except for the amoxicillin-chocolate pudding mixture. Three household containers (cups, plates, and bowls) and four mixing times (0.5 min, 1 min, 2 min, and 5 min) were found to be suitable for preparation of homogeneous mixtures of the antibiotics and foods. For practical purposes, 1 to 2 min mixing time is sufficient to produce homogeneous mixtures. The results of this study provided product quality data on the interactions between the antibiotics and the foods and can potentially support future development of home preparation instructions of antibiotics for pediatric patients or patients with swallowing difficulties.


Assuntos
Antibacterianos , Preferências Alimentares , Adulto , Humanos , Criança , Clindamicina , Doxiciclina , Química Farmacêutica/métodos , Comprimidos , Amoxicilina , Solubilidade , Cápsulas
2.
Breast Cancer Res Treat ; 197(2): 307-317, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36396775

RESUMO

PURPOSE: Increased body mass index (BMI) and metabolic syndrome (MS) are associated with increased breast cancer recurrence risk. Whether this is due to intrinsic tumor biology or modifiable factors of the obese state remains incompletely understood. METHODS: Oncotype DX Recurrence Scores of 751 patients were stratified by BMI to assess association with tumor-intrinsic recurrence risk. Cellular proliferation by Ki67 after 10-21 days of presurgical letrozole treatment was used to stratify endocrine therapy response (sensitive-ln(Ki67) < 1; intermediate-ln(Ki67)1-2; resistant-ln(Ki67) > = 2). BMI at the time of surgery and MS variables were collected retrospectively for 143 patients to analyze association between therapy response and BMI/MS. Additionally, PI3K pathway signaling was evaluated by immunohistochemistry of phosphorylated Akt and S6. RESULTS: There was no significant association between BMI and recurrence score (p = 0.99), and risk score distribution was similar across BMI groups. However, BMI was associated with short-term endocrine therapy resistance, with a significant enrichment of intermediate and resistant tumors in patients with obesity (55%, p = 0.0392). Similarly, the relative risk of an endocrine therapy-resistant tumor was 1.4-fold greater for patients with MS (p = 0.0197). In evaluating PI3K pathway mediators, we found patients with 3 or more MS criteria had more tumors with pAkt scores above the median (p = 0.0436). There were no significant differences in S6 activation. CONCLUSION: Our findings suggest the association between obesity/metabolic syndrome and breast cancer recurrence is better reflected by response to treatment than tumor-intrinsic properties, suggesting interventions to reverse obesity and/or MS may improve outcomes for breast cancer recurrence.


Assuntos
Neoplasias da Mama , Síndrome Metabólica , Humanos , Feminino , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Antígeno Ki-67 , Síndrome Metabólica/complicações , Estudos Retrospectivos , Fosfatidilinositol 3-Quinases/metabolismo , Recidiva Local de Neoplasia/patologia , Obesidade/complicações , Biomarcadores Tumorais/metabolismo
3.
BMJ Glob Health ; 6(8)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34452940

RESUMO

INTRODUCTION: Household air pollution from solid fuel combustion for cooking and heating is a leading cause of childhood morbidity and mortality worldwide. We hypothesised that clean cooking interventions delivered during pregnancy would improve child health. METHODS: We conducted a cluster randomised trial in rural Ghana to test whether providing pregnant women liquefied petroleum gas (LPG) cookstoves or improved biomass cookstoves would reduce personal carbon monoxide and fine particulate pollution exposure, increase birth weight and reduce physician-assessed severe pneumonia in the first 12 months of life, compared with control participants who continued to cook with traditional stoves. Primary analyses were intention-to-treat. The trial was registered with ClinicalTrials.gov and follow-up is complete. RESULTS: Enrolment began on 14 April 2014, and ended on 20 August 2015. We enrolled 1414 pregnant women; 361 in the LPG arm, 527 in the improved biomass cookstove arm and 526 controls. We saw no improvement in birth weight (the difference in mean birth weight for LPG arm births was 29 g lighter (95% CI -113 to 56, p=0.51) and for improved biomass arm births was 9 g heavier (95% CI -64 to 82, p=0.81), compared with control newborns) nor severe child pneumonia (the rate ratio for pneumonia in the LPG arm was 0.98 (95% CI 0.58 to 1.70; p=0.95) and for the improved biomass arm was 1.21 (95% CI 0.78 to 1.90; p=0.52), compared with the control arm). Air pollution exposures in the LPG arm remained above WHO health-based targets (LPG median particulate matter less than 2.5 microns in diameter (PM2.5) 45 µg/m³; IQR 32-65 vs control median PM2.5 67 µg/m³, IQR 46-97). CONCLUSIONS: Neither prenatally-introduced LPG nor improved biomass cookstoves improved birth weight or reduced severe pneumonia risk in the first 12 months of life. We hypothesise that this is due to lower-than-expected exposure reductions in the intervention arms. TRIAL REGISTRATION NUMBER: NCT01335490.


Assuntos
Poluição do Ar em Ambientes Fechados , Utensílios Domésticos , Poluição do Ar em Ambientes Fechados/análise , Culinária , Feminino , Gana/epidemiologia , Humanos , Lactente , Saúde do Lactente , Recém-Nascido , Gravidez
4.
Int J Pharm ; 604: 120677, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33961953

RESUMO

The physical and chemical stability of therapeutic peptides presents challenges in developing robust formulations. The stability of the formulation affects product safety, efficacy and quality. Therefore, an understanding of the effects of formulation variables on the peptide's conformational structure and on its possible physical and chemical degradation is vital. To this end, computational and experimental analysis were employed to investigate the impact of formulation, peptide folding and product handling on oxidation, fibrillar aggregation and gelation of teriparatide. Teriparatide was used as a model drug due to the correlation of its conformation in solution with its pharmacological activity. Fibrillar aggregation and gelation were monitored using four orthogonal techniques. An innovative, automated platform coupled with ion mobility mass spectrometry was used for profiling chemical degradants. Increases in teriparatide concentration, pH, and ionic strength were found to increase the rate of fibrillar aggregation and gelation. Conversely, an increase in peptide folding and stabilization of the folded structures was found to decrease the rate of fibrillar aggregation and gelation. Moreover, the rate of oxidation was found to be inversely related to its solution concentration and extent of peptide folding. The present study provides an insight into formulation strategies designed to reduce the potential risk of physical and chemical degradation of peptides with a defined conformation.


Assuntos
Peptídeos , Conformação Molecular , Concentração Osmolar , Oxirredução
5.
Pharm Nanotechnol ; 8(2): 108-132, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32091350

RESUMO

BACKGROUND: Combination chemotherapy capable of overcoming cancer drug resistance can be facilitated by nanotechnology. OBJECTIVE: Synthesis, characterization, statistical experimental design, analysis and optimization of stealth pH-sensitive polymeric nanoparticles suitable as a platform for simultaneous delivery of paclitaxel and 17-AAG in breast cancer therapy were investigated. METHODS: An acetal crosslinker and a poly(ɛ)caprolactone macromonomer were synthesized and characterized. The statistical experimental design used was the response surface method (RSM). We used the central composite face-centered design (CCF) in three independent factors and seventeen runs. Nanoparticles were fabricated by dispersion polymerization techniques. Response variables evaluated were: particle size, drug loading, encapsulation efficiency, and in vitro availability. RESULTS: Scanning electron micrographs showed the formation of spherical nanoparticles. Computer software was used for the analysis of variance with a 95% confidence level and Q2 (goodness of prediction) to select an appropriate model for each of the response variables. Each term in each of the models was tested for the significance of the regression coefficients. The computer software optimizer was used for optimization to select factor combination to minimize particle size, time (h) for maximum release of paclitaxel and 17-AAG, to maximize paclitaxel and 17-AAG loading efficiency and to maximize paclitaxel and 17-AAG encapsulation efficiency. CONCLUSION: The optimization was successful, as shown by the validation data which lie within the confidence intervals of predicted values of the response variables. The selected factor combination is suitable for the in vivo evaluation of the nanoparticles loaded with paclitaxel and 17-AAG.


Assuntos
Antineoplásicos Fitogênicos/farmacocinética , Benzoquinonas/farmacologia , Lactamas Macrocíclicas/farmacologia , Paclitaxel/farmacocinética , Polímeros/química , Antineoplásicos Fitogênicos/química , Benzoquinonas/química , Cápsulas , Desenho Assistido por Computador , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Lactamas Macrocíclicas/química , Nanopartículas , Paclitaxel/química , Tamanho da Partícula , Propriedades de Superfície
6.
PLoS One ; 7(4): e34073, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22514617

RESUMO

BACKGROUND: WHO now recommends test-based management of malaria across all transmission settings. The accuracy of rapid diagnostic test (RDT) and the outcome of treatment based on the result of tests will influence acceptability of and adherence to the new guidelines. METHOD: We conducted a study at the Kintampo hospital in rural Ghana to evaluate the performance of CareStart, a HRP-2 based RDT, using microscopy as reference. We applied IMCI treatment guidelines, restricted ACT to RDT-positive children and followed-up both RDT-positive (malaria) and RDT-negative (non-malaria) cases over 28 days. RESULTS: 436 children were enrolled in the RDT evaluation and 391 (children with haemoglobin >8.0 gm/dl) were followed-up to assess treatment outcomes. Mean age was 25.4 months (s.d. 14.6). Sensitivity and specificity of the RDT were 100.0% and 73.0% respectively. Over the follow-up period, 32 (18.5%) RDT-negative children converted to positive, with 7 (4.0%) of them presenting with fever. More children in the non-malaria group made unscheduled visits than children in the malaria group (13.3% versus 7.7%) On all scheduled follow-up visits, proportion of children having a temperature higher than that recorded on day 0 was higher in the non-malaria group compared to the malaria group. Reports of unfavourable treatment outcomes by caregivers were higher among the non-malaria group than the malaria group. CONCLUSIONS: The RDT had good sensitivity and specificity. However a minority of children who will not receive ACT based on RDT results may develop clinical malaria within a short period in high transmission settings. This could undermine caregivers' and health workers' confidence in the new guidelines. Improving the quality of management of non-malarial febrile illnesses should be a priority in the era of test-based management of malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT00832754.


Assuntos
Testes Diagnósticos de Rotina/métodos , Febre/diagnóstico , Malária/diagnóstico , Pré-Escolar , Feminino , Gana , Humanos , Masculino , Sensibilidade e Especificidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...