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1.
Nutr Clin Pract ; 36(6): 1106-1125, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34705289

RESUMO

Lipid injectable emulsions (ILEs) are complex pharmaceutical formulations intended as a source of energy and fatty acids for parenteral nutrition (PN) therapy. Part 1 of this series addressed issues associated with and safety recommendations pertaining to adult ILE use. Part 2 addresses ILE safety in neonatal and pediatric patients. Considerations for ILE use in the neonatal and pediatric populations differ from those of adults. For example, these patients often require higher doses compared with adult counterparts to support growth, development, and daily metabolic needs. ILE is also frequently administered as a separate infusion as opposed to in a total nutrient admixture owing to compatibility and stability issues and limitations to intravenous access in the neonatal and pediatric populations. ILE is the most frequent PN ingredient associated with PN errors occurring in the administration, prescribing, and transcribing processes. Concerns exist with use of in-line filters and repackaging of commercial products for infusion. ILE use in neonatal and pediatric patients has been associated with both minor and major adverse effects, which most often occur with doses exceeding manufacturer recommendations. Gaps in ILE best practices for neonatal and pediatric patients predispose to errors in the PN use system. This paper describes safe-use considerations for ILE products available in the United States in neonatal and pediatric patients, including indications, prescribing, order review, preparation, administration, and monitoring. This paper has been approved by the American Society for Parenteral and Enteral Nutrition (ASPEN) Board of Directors.


Assuntos
Emulsões Gordurosas Intravenosas , Nutrição Parenteral , Adulto , Criança , Nutrição Enteral , Emulsões Gordurosas Intravenosas/efeitos adversos , Ácidos Graxos , Humanos , Recém-Nascido , Soluções de Nutrição Parenteral , Estados Unidos
2.
Nutr Clin Pract ; 35(5): 769-782, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32460429

RESUMO

Lipid injectable emulsions (ILEs) are complex pharmaceutical formulations used as a source of energy and essential fatty acids in parenteral nutrition. Issues associated with ILE use are distinctly different from oral fat and arise from emulsion stability, dose, and infusion tolerance. Since 1975, soybean oil has been the consistent source oil used in ILE formulations in the US. Partly because of safety concerns with the soybean-based ILE and frequent and long-standing problems with product inventory shortages, new ILE products have become available. Gaps in ILE best practices create a risk for ILE safety errors in prescribing, compounding, and administration of these products. This paper provides information on appropriate indications, dosing, and methods to avoid potential errors with ILE products in the US. This paper (Part 1) will focus on ILE background, information, and recommendations for adult patients, whereas Part 2 of this series will focus on neonatal and pediatric patient-specific information.


Assuntos
Emulsões Gordurosas Intravenosas/administração & dosagem , Soluções de Nutrição Parenteral/administração & dosagem , Nutrição Parenteral/normas , Adulto , Estado Terminal/terapia , Composição de Medicamentos , Ácidos Graxos Essenciais , Óleos de Peixe/administração & dosagem , Humanos , Azeite de Oliva/administração & dosagem , Óleo de Soja/administração & dosagem , Triglicerídeos/administração & dosagem , Estados Unidos
3.
Pharm Pract (Granada) ; 17(2): 1416, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275493

RESUMO

BACKGROUND: Lack of benefit and potential harm of early parenteral nutrition (PN) initiation in critically ill children was highlighted in the 2016 published results of a large multicenter, randomized controlled trial. OBJECTIVES: The purpose of this project was to implement a process to delay PN initiation for up to five days after admission to our pediatric intensive care unit (PICU). METHODS: Patients greater than thirty days of age, admitted to the PICU beginning July 1, 2016 were included in the analysis of the healthcare improvement initiative to decrease early PN initiation. A meeting was held with PICU fellows, attending physicians, dietitians, and pharmacists to reach a consensus to delay initiation of parenteral nutrition until PICU day five. The dietitian, with pharmacist support, reiterated recommendations on rounds and in formal notes. RESULTS: A total of 2333 patients were identified in the pre-intervention group and a total of 2491 patients in the post-intervention group. The percentage of patients receiving PN prior to day five within the PICU was 5.5% in the pre-intervention group versus 3.1% in the delayed PN group (p<0.001). PICU patients receiving PN less than or equal to three days decreased from 2.6% pre-intervention to 1.5% post-intervention (p=0.01). For the subset of patients who were initiated on PN after admission to the PICU, median PICU length of stay was 7 days versus 6 days in the pre-intervention versus post-intervention group (p=0.26). CONCLUSIONS: Decrease in PN utilization was seen in the pre and post-intervention groups as assessed by percentage of patients initiated on PN prior to day five of PICU admission. Consensus among practitioners with consistent recommendations from the frontline dietitian and pharmacist, with nutrition support team collaboration, contributed to the evidence based quality initiative results. Delaying PN did not adversely affect length of stay pre versus post-intervention.

4.
Am J Health Syst Pharm ; 76(11): 815-819, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31361813

RESUMO

PURPOSE: The study analyzes the effectiveness and safety of a higher than standard enoxaparin dosing protocol implemented for pediatric patients requiring initiation of therapeutic anticoagulation. METHODS: A retrospective review of 2 enoxaparin dosing and monitoring protocols was performed. The standard protocol used 1.5 mg/kg/dose (in patients <3 months of age) and 1 mg/kg/dose (in patients ≥3 months of age) with anti-Xa monitoring following the first dose. The high-dose protocol was implemented at 1.7 mg/kg/dose (in patients <3 months of age), 1.5 mg/kg/dose (in patients 3 through 11 months of age), 1.2 mg/kg/dose (in patients 1 through 4 years of age), and 1.1 mg/kg/dose (in patients 5 through 17 years of age), with anti-Xa monitoring after the second dose. Primary outcomes were number of dosing changes prior to and time to first target anti-Xa level. Secondary outcomes included percentage of patients with anti-Xa levels above target level. RESULTS: The median number of dose changes required to achieve a target anti-Xa level was 1 (interquartile range [IQR], 0-1.5) and 0 (IQR, 0-1) for the standard-dose (n = 87) and high-dose groups (n = 132) (p = 0.17), respectively. The median number of dose adjustments to achieve target anti-Xa levels in the 3 through 11 months of age subgroup declined from 2 (IQR, 1-3.25) to 0 (IQR, 0-1) in the standard- versus high-dose groups, respectively (p < 0.01). No difference was seen in other age subgroups. Patients with above-target levels did not differ statistically between groups. CONCLUSION: Initiating enoxaparin at higher doses in pediatric patients may result in fewer dosing changes than standard dosing. Benefit was demonstrated for the 3-11 months of age high-dose subgroup. Across all groups, the high-dose strategy was safe and did not result in a statistically significant increase in above-target levels.


Assuntos
Monitoramento de Medicamentos/métodos , Enoxaparina/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Adolescente , Coagulação Sanguínea/efeitos dos fármacos , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Enoxaparina/efeitos adversos , Enoxaparina/sangue , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/sangue , Feminino , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Lactente , Masculino , Estudos Retrospectivos
5.
Pharm. pract. (Granada, Internet) ; 17(2): 0-0, abr.-jun. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-184675

RESUMO

Background: Lack of benefit and potential harm of early parenteral nutrition (PN) initiation in critically ill children was highlighted in the 2016 published results of a large multicenter, randomized controlled trial. Objectives: The purpose of this project was to implement a process to delay PN initiation for up to five days after admission to our pediatric intensive care unit (PICU). Methods: Patients greater than thirty days of age, admitted to the PICU beginning July 1, 2016 were included in the analysis of the healthcare improvement initiative to decrease early PN initiation. A meeting was held with PICU fellows, attending physicians, dietitians, and pharmacists to reach a consensus to delay initiation of parenteral nutrition until PICU day five. The dietitian, with pharmacist support, reiterated recommendations on rounds and in formal notes. Results: A total of 2333 patients were identified in the pre-intervention group and a total of 2491 patients in the post-intervention group. The percentage of patients receiving PN prior to day five within the PICU was 5.5% in the pre-intervention group versus 3.1% in the delayed PN group (p<0.001). PICU patients receiving PN less than or equal to three days decreased from 2.6% pre-intervention to 1.5% post-intervention (p=0.01). For the subset of patients who were initiated on PN after admission to the PICU, median PICU length of stay was 7 days versus 6 days in the pre-intervention versus post-intervention group (p=0.26). Conclusions: Decrease in PN utilization was seen in the pre and post-intervention groups as assessed by percentage of patients initiated on PN prior to day five of PICU admission. Consensus among practitioners with consistent recommendations from the frontline dietitian and pharmacist, with nutrition support team collaboration, contributed to the evidence based quality initiative results. Delaying PN did not adversely affect length of stay pre versus post-intervention


No disponible


Assuntos
Humanos , Nutrição Enteral/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , Cuidados Críticos/métodos , Tempo de Internação/estatística & dados numéricos , Serviço de Farmácia Hospitalar/métodos , Estudos Retrospectivos , Equipe de Assistência ao Paciente/organização & administração
6.
Nutr Clin Pract ; 32(4): 552-556, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28760114

RESUMO

BACKGROUND: Pediatric patients who are receiving parenteral nutrition (PN) unsupplemented with trace minerals can become deficient. Due to shortages in trace mineral products and the 2004 American Society for Parenteral and Enteral Nutrition report stating that individualized trace element supplementation may be warranted, a review was conducted concerning the trace minerals selenium (Se), manganese (Mn), and iodine (I). METHOD: A retrospective review of pediatric patients receiving PN that contained Se and Mn was conducted to determine if a difference existed between them and patients receiving PN without Se and Mn. Statistical analysis was done to assess a difference between trace mineral levels and the time to deficiency between supplemented and unsupplemented patients. Unsupplemented I patients had urine I levels assessed to determine deficiencies in patients receiving PN. RESULTS: Plasma Se levels were measured at a mean of 20 days for supplemented patients (n = 131) and 19 days for nonsupplemented patients (n = 57) with no difference between groups ( P = .2973). Plasma Mn levels were measured at a mean of 28 days, showing no statistical difference ( P = .721). Of the 177 nonsupplemented I patients, 74% demonstrated I deficiencies without supplementation. CONCLUSIONS: Time to the development of a Se, Mn, or I deficiency is important to guide supplementation of exclusive PN in children when trace mineral products are short in supply. Our retrospective experience supports assessment of the trace minerals Se at 21 days and Mn at 30 days. It also suggests that some pediatric patients receiving PN are deficient in I.


Assuntos
Iodo/urina , Manganês/sangue , Nutrição Parenteral , Selênio/sangue , Adolescente , Criança , Pré-Escolar , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Nutrição Enteral , Humanos , Lactente , Recém-Nascido , Iodo/administração & dosagem , Iodo/deficiência , Manganês/administração & dosagem , Manganês/deficiência , Avaliação Nutricional , Política Nutricional , Necessidades Nutricionais , Estudos Retrospectivos , Selênio/administração & dosagem , Selênio/deficiência , Oligoelementos/administração & dosagem , Oligoelementos/sangue , Oligoelementos/deficiência
7.
Int J Pharm Compd ; 20(5): 435-437, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28339379

RESUMO

Sodium nitroprusside is a potent vasodilator employed intraoperatively and within critical care areas. The photolabile pharmaceutical agent has been used for decades and various stability studies have been executed. Due to potential shortages and the desire to batch compound sodium nitroprusside at a concentration of 1 mg/mL in polypropylene syringes, a new stability study was performed. Chromatographic analysis was conducted on a C18 column, with elution via an aqueous phase of 0.01 M sodium phosphate monobasic, adjusted to pH 6.5 with sodium hydroxide, and methanol (97.5:2.5) at a rate of 1 mL/min, and subsequent ultraviolet detection at 210 nm. Triplicate determinations of four samples, stored under refrigeration at 4°C, were obtained initially and on days 2, 5, and 9. Turbidity and pH measurements were performed in conjunction with visual observation on days of chromatographic analysis. Results demonstrate that sodium nitroprusside compounded in 5% dextrose at a concentration of 1 mg/mL, stored at 4°C protected from light in polypropylene syringes, is physically and chemically stable for at least 9 days.


Assuntos
Glucose/análise , Nitroprussiato/análise , Vasodilatadores/análise , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Concentração de Íons de Hidrogênio , Luz , Nefelometria e Turbidimetria , Refrigeração , Seringas , Temperatura
8.
Int J Pharm Compd ; 19(4): 344-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26625573

RESUMO

Chemotherapy induced nausea and vomiting is problematic for many patients undergoing chemotherapy. Multiple-drug treatments have been developed to mitigate chemotherapy induced nausea and vomiting. A patient-controlled infusion of diphenhydramine hydrochloride, lorazepam, and dexamethasone sodium phosphate has been studied in patients who are refractory to first-line therapy. Unfortunately, the physical and chemical compatibility of this three-drug combination is not available in the published literature. Chemical compatibility was evaluated using high-performance liquid chromatography with ultraviolet detection. Visual observation was employed to detect change in color, clarity, or gas evolution. Turbidity and pH measurements were performed in conjunction with visual observation at hours 0, 24, and 48. Results showed that diphenhydramine hydrochloride 4 mg/mL, lorazepam 0.16 mg/mL, and dexamethasone sodium phosphate 0.27 mg/mL in 0.9% sodium chloride stored in polypropylene syringes were compatible, and components retained greater than 95% of their original concentration over 48 hours when stored at room temperature.


Assuntos
Dexametasona/análogos & derivados , Difenidramina/química , Lorazepam/química , Dexametasona/química , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Polipropilenos , Cloreto de Sódio/química , Seringas
9.
J Nat Prod ; 78(3): 476-85, 2015 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-25689568

RESUMO

The first 23-step total synthesis of the cyclodepsipeptide dolastatin 16 (1) has been achieved. Synthesis of the dolaphenvaline and dolamethylleuine amino acid units using simplified methods improved the overall efficiency. The formation of the 25-membered macrocycle employing lactonization with 2-methyl-6-nitrobenzoic anhydride completed a key step in the synthesis. Regrettably, the synthetic dolastatin 16 (1), while otherwise identical (by X-ray crystal structure and spectral analyses) with the natural product, did not reproduce the powerful (nanomolar) cancer cell growth inhibition displayed by the natural isolate. Presumably this result can be attributed to conformation(s) of the synthetic dolastatin 16 (1) or to a chemically undetected component isolated with the natural product.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Depsipeptídeos/síntese química , Depsipeptídeos/farmacologia , Anidridos/química , Antineoplásicos/química , Depsipeptídeos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Conformação Molecular , Estrutura Molecular , Nitrobenzoatos/química , Ressonância Magnética Nuclear Biomolecular , Células Tumorais Cultivadas
10.
Am J Health Syst Pharm ; 72(4): 285-9, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25631835

RESUMO

PURPOSE: Correlations between the i.v. immune globulin (IVIG) dose and the change in serum immunoglobulin G (IgG) concentration with three methods of weight-based dosing were investigated. METHODS: A retrospective medical records review was conducted to identify patients in a multicenter healthcare system who received IVIG over a 10-year period and had serum IgG measurements within two days before and two days after the date of IVIG administration. For each of the 11 adults and 7 adolescents identified, the relationship between the weight-based dose of IVIG (determined using actual body weight [BW], adjusted BW, or ideal BW [IBW]) and the resulting change in serum IgG was evaluated. Correlation coefficients and corresponding p values for the three dosing methods were calculated and compared. RESULTS: Among adult patients, the correlation of IVIG dose and postdose change in serum IgG was strongest with dosing by IBW (correlation coefficient [r], 0.83 [p < 0.05] versus r values of 0.73 and 0.70 for dosing by adjusted BW or actual BW, respectively [p = 0.05 for both]); the corresponding r values in adolescent patients were 0.99, 0.99, and 0.95, respectively (p < 0.005 for all). There were no statistically significant differences between the r values calculated for the three weight-based dosing methods in either adults or adolescents. CONCLUSION: In adult patients, the correlation between the dose of IVIG and the change in IgG level was strongest when doses were calculated using IBW; comparable degrees of correlation were observed with the three evaluated methods of weight-based dosing in the adolescent population.


Assuntos
Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/farmacologia , Adolescente , Adulto , Peso Corporal , Criança , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Am J Health Syst Pharm ; 69(7): 595-7, 2012 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-22441792

RESUMO

PURPOSE: The results of a study to determine the long-term (up to 14 days) stability of diluted dexmedetomidine kept in polypropylene syringes under typical pharmacy storage conditions are presented. METHODS: Four samples of dexmedetomidine injection diluted to 4 µg/mL in 0.9% sodium chloride were prepared and divided into 25-mL portions for storage in syringes at ambient room temperature (20-25 °C) with light exposure or under refrigeration (5 °C) in darkness. At 24 and 48 hours, the percentage of the initial dexmedetomidine concentration remaining in all samples was assessed via high-performance liquid chromatography with diode-array detection; further stability testing of the refrigerated samples was performed on days 7 and 14. At each time point, the test samples were visually inspected for color, clarity, and signs of formation of particulate matter. RESULTS: As determined by chromatographic analyses, the samples of diluted dexmedetomidine stored in syringes at room temperature exhibited a loss of drug concentration of <10% over 48 hours; the refrigerated samples exhibited a loss of drug concentration of <5% over 14 days. All of the syringe-stored samples remained clear and colorless on visual inspection for the duration of the study. CONCLUSION: Dexmedetomidine diluted to 4 µg/mL in 0.9% sodium chloride injection was stable for at least 48 hours at 20-25 °C and 14 days at 5 °C when stored in polypropylene syringes.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/química , Dexmedetomidina/química , Cromatografia Líquida de Alta Pressão , Dexmedetomidina/análise , Estabilidade de Medicamentos , Polipropilenos , Seringas
12.
J Nat Prod ; 74(5): 1003-8, 2011 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-21539315

RESUMO

Three advances necessary to bring dolastatin 16 (1) into full-scale preclinical development as an anticancer drug have been accomplished. The X-ray crystal structure of dolastatin 16 has been solved, which allowed stereoselective syntheses of its two new amino acid units, dolamethylleuine (Dml) and dolaphenvaline (Dpv), to be completed. The X-ray crystal structures of synthetic Z-Dml and TFA-Dpv have also been completed.


Assuntos
Antineoplásicos , Depsipeptídeos , Antineoplásicos/química , Antineoplásicos/farmacologia , Cristalografia por Raios X , Depsipeptídeos/síntese química , Depsipeptídeos/química , Depsipeptídeos/farmacologia , Estrutura Molecular
13.
J AOAC Int ; 89(6): 1591-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17225607

RESUMO

A gas chromatography-mass spectrometry (GC/MS) method is described for the easy rapid determination and simultaneous confirmation of the biogenic amines putrescine (PUT), cadaverine (CAD), histamine (HTA), and spermidine (SPD) in fresh frozen tuna loin. The method can also be used to monitor tyramine (TYR). The method involves homogenization of fish tissue, extraction of biogenic amines into trichloroacetic acid solution, centrifugation, alkalization, and derivatization of supernatant with ethylchloroformate. All seafood species were fortified to contain 2.5, 5.0, 10.0, 12.5, and 25.0 microg/g (ppm) PUT, CAD, and SPD; and 10.0, 20.0, 40.0, 50.0, and 100.0 microg/g (ppm) HTA. Determination was based on standard curves for each analyte using peak areas with matrix standards equivalent to a concentration range bracketing the spike level. A set of 5 matrix controls (unfortified tuna tissue) was also analyzed; only endogenous SPD was found in all samples. The interassay average recoveries ranged from 57 to 79% across analytes and spike levels.


Assuntos
Aminas Biogênicas/análise , Ésteres do Ácido Fórmico/química , Carne/análise , Atum/metabolismo , Animais , Calibragem , Cromatografia Gasosa-Espectrometria de Massas , Indicadores e Reagentes , Padrões de Referência , Reprodutibilidade dos Testes , Tiramina/análise
14.
J Chromatogr A ; 1094(1-2): 60-9, 2005 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-16257290

RESUMO

A liquid chromatography (LC) method is described for the easy determination of the biogenic diamines putrescine (PUT) and cadaverine (CAD) in canned tuna, frozen tuna loin, fresh mahimahi fillet, frozen raw shrimp, cooked lump crabmeat, and fresh and cold-smoked salmon. The method is also a useful screen for histamine (HTA). The method involves homogenization of fish tissue, extraction of biogenic amines into borate-trichloroacetic acid solution, centrifugation, and derivatization of supernatant with 1-pyrenebutanoic acid succinimidyl ester. The derivatized diamine species allow for the intramolecular excimer fluorescence of the pyrene moiety at a higher emission wavelength than is possible for the endogenous tissue monoamines, thus providing visual specificity of detection. All seafood species were fortified with 0.5, 1.0, 5.0, 10.0, and 15.0 microg/g (ppm) of PUT and CAD. Determination was based on standard graphs for PUT and CAD using peak areas with standard solutions equivalent to 0.375, 1.0, 5.0, 10.0, and 20.0 ppm in tissue. A set of five matrix controls (unfortified seafood tissue) were also analyzed; endogenous PUT was found in all samples except the canned tuna, and CAD found only in the shrimp, crab, and cold-smoked salmon. The background amines were thus subtracted prior to determining spike recovery. The intra-assay average recoveries ranged from 71 to 94% across species and spike levels.


Assuntos
Cadaverina/análise , Putrescina/análise , Pirenos/química , Alimentos Marinhos/análise , Espectrometria de Fluorescência/métodos , Animais
15.
J Agric Food Chem ; 53(18): 7019-23, 2005 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-16131105

RESUMO

A simple and confirmative method for quantitative determination of carbon monoxide in tuna and mahi-mahi tissues using GC/MS, following chemical liberation of CO into headspace, is described. Carbon monoxide in recent years has been employed by the fishery industry to preserve fresh appearance in selected species of finfish during frozen storage, particularly in vacuum-packaged products. Indigenous CO contents of fresh Ahi tuna and mahi-mahi were examined using the method described in this study and found to be close to or less than 150 and 100 ng/g, respectively. Commercially CO-treated, vacuum-packaged tuna from multiple sources consistently showed CO level near or greater than 1 mug/g, while CO level in the only CO-treated frozen mahi-mahi sample was in the 500 ng/g range. The difference between untreated and treated specimens was in the range of 1 order of magnitude and thus suggested an easy quantitative and confirmative method of CO using widely available instrumentation that may be potentially useful for regulatory purpose in determining whether a commercially available product has been exposed to CO even if not labeled as such.


Assuntos
Monóxido de Carbono/análise , Conservação de Alimentos , Cromatografia Gasosa-Espectrometria de Massas , Perciformes , Atum , Animais , Vácuo
16.
J Nat Prod ; 68(8): 1191-7, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16124759

RESUMO

Further structure-activity relationship (SAR) exploration of 3,4-methylenedioxy-5,4'-dimethoxy-3'-amino-Z-stilbene (1a) derivatives resulted in the efficient synthesis of tyrosine amide hydrochloride 9, two tyrosine amide phosphate prodrugs (3a and 6), and sodium aspartate amide 11. Two additional cancer cell growth inhibitors (14 and 16) were synthesized by employing peptide coupling between amine 1a and the Dap unit of dolastatin 10 (4a) to yield amide 14 followed by Dov-Val-Dil (15) to yield peptide 16. The latter represents a combination of stilbene 1a with the des-Doe tetrapeptide unit of the powerful tubulin assembly inhibitor dolastatin 10. Peptide 16 was examined for potential binding to tubulin in the vinca and/or colchicine regions and found to perform primarily as a relative of dolastatin 10. Amide 14 had anticryptococcal and antibacterial activities.


Assuntos
Antineoplásicos/síntese química , Dioxóis/síntese química , Estilbenos/síntese química , Tirosina/síntese química , Amidas/síntese química , Amidas/química , Amidas/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Colchicina , Depsipeptídeos , Dioxóis/química , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores do Crescimento , Humanos , Mitose/efeitos dos fármacos , Estrutura Molecular , Oligopeptídeos/farmacologia , Estereoisomerismo , Estilbenos/química , Relação Estrutura-Atividade , Tubulina (Proteína)/química , Células Tumorais Cultivadas , Tirosina/análogos & derivados , Tirosina/química , Tirosina/farmacologia
17.
J Chromatogr A ; 1075(1-2): 23-32, 2005 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-15974114

RESUMO

The extraction and cleanup of commonly used tetracyclines (oxytetracycline, tetracycline, chlortetracycline, and doxycycline) from sample matrix, and their subsequent determination via liquid chromatography can be problematic. Many manuscripts report on various challenges encountered when developing a method for tetracycline antibiotics determination. These complexities often result in less than perfect recoveries or chromatograms and are based on the underlying chemistry associated with tetracyclines. This review compiles, compares, and discusses the results and observations found in published methods, while focusing on chemical principles in order to increase the practicing chemist's understanding of TCs to aid him/her in developing useful analyses.


Assuntos
Cromatografia Líquida/métodos , Tetraciclina/análise , Solubilidade
18.
J AOAC Int ; 88(2): 505-10, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15859078

RESUMO

A liquid chromatography (LC) method is described for the determination of oxytetracycline (OTC) in farmed Atlantic salmon muscle tissue. The method involves homogenization of salmon tissue, extraction of OTC into Mcllvaine-EDTA buffer, acid precipitation of proteins, cleanup through tandem solid-phase extraction cartridges (Strata-X and aminopropyl), elution with mobile phase containing slightly alkaline buffer and Mg2+, and LC separation with metal-chelate induced fluorescence detection. Salmon tissue was fortified with 0.10, 0.25, 0.50, 0.75, and 1.0 microg/g (ppm) oxytetracycline. Average absolute recoveries were 84, 76, 70, 76, and 85%, respectively, with relative standard deviation (RSD) values all less than 9%. The interassay average recovery was 78%, with a 4.2% RSD. Determination was based on a standard graph using peak areas with standard solutions equivalent to 0.0625, 0.125, 0.25, 0.50, and 1.0 ppm in tissue. A set of 5 matrix controls (unfortified salmon tissue) were also analyzed, in which no OTC was detected. The lowest standard was used as the limit of quantitation.


Assuntos
Antibacterianos/análise , Carne/análise , Músculo Esquelético/química , Oxitetraciclina/análise , Salmão/metabolismo , Animais , Calibragem , Cromatografia Líquida , Corantes Fluorescentes , Indicadores e Reagentes , Controle de Qualidade , Padrões de Referência , Reprodutibilidade dos Testes , Soluções , Solventes , Espectrometria de Fluorescência
19.
J Med Chem ; 46(4): 525-31, 2003 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-12570374

RESUMO

An efficient synthesis of 3,4-methylenedioxy-5,4'-dimethoxy-3'-amino-Z-stilbene (1c) and hydrochloride (1d) is reported. The nitrostilbene intermediate 6a was obtained via a Wittig reaction using phosphonium salt 4 and 3-nitro-4-methoxybenzaldehyde 5. A one-step reduction using zinc in acetic acid produced the synthetic objective amine 1c. The coupling of this amine with various Fmoc amino acids, followed by cleavage of the alpha-amine protecting group, resulted in a series of new cancer cell growth inhibitory amides. Amine 1c, hydrochloride 1d, glycine amide 3b, and tyrosine amide 3f had the highest level (GI50 = 10(-2)-10(-3) micro g/mL) of activity against a panel of six human and one animal (P388) cancer cell lines. Amine 1c and its hydrochloride 1d potently inhibited tubulin polymerization by binding at the colchicine site, while the amides had little activity against purified tubulin. Nevertheless, most of the amides caused a marked increase in the mitotic index of treated cells, indicating that tubulin was their intracellular target.


Assuntos
Aminoácidos/síntese química , Antineoplásicos/síntese química , Dioxóis/síntese química , Estilbenos/síntese química , Amidas/síntese química , Amidas/química , Amidas/farmacologia , Aminoácidos/química , Aminoácidos/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Biopolímeros , Dioxóis/química , Dioxóis/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Mitose/efeitos dos fármacos , Estilbenos/química , Estilbenos/farmacologia , Relação Estrutura-Atividade , Tubulina (Proteína)/química , Células Tumorais Cultivadas
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