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1.
J Zoo Wildl Med ; 55(1): 73-85, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38453490

RESUMO

Firocoxib is a COX-2-selective nonsteroidal anti-inflammatory drug (NSAID) with limited effects on COX-1, which means it likely has fewer side effects than typically associated with other NSAIDs. This study determined possible doses of firocoxib based on single- and multidose pharmacokinetic trials conducted in 10 Asian elephants (Elephas maximus). Initially, two single oral dose trials (0.01 and 0.1 mg/kg) of a commercially available tablet (n = 6) and paste (n = 4) formulation were used to determine a preferred dose. The 0.1 mg/kg dose was further evaluated via IV single dose (n = 3) and oral multidose trials (tablets n = 6; paste n = 4). Serum peak and trough firocoxib concentrations were also evaluated in Asian elephants (n = 4) that had been being treated for a minimum of 90 consecutive days. Key pharmacokinetic parameters for the 0.1 mg/kg single-dose trials included mean peak serum concentrations of 49 ± 3.3 ng/ml for tablets and 62 ± 14.8 ng/ml for paste, area under the curve (AUC) of 1,332 ± 878 h*mg/ml for tablets and 1,455 ± 634 h*mg/ml for paste, and half-life (T1/2) of 34.3 ± 30.3 h for tablets and 19.9 ± 12.8 h for paste. After 8 d of dosing at 0.1 mg/kg every 24 h, pharmacokinetic parameters stabilized to an AUC of 6,341 ± 3,003 h*mg/ml for tablets and 5,613 ± 2,262 for paste, and T1/2 of 84.4 ± 32.2 h for tablets and 62.9 ± 2.3 h for paste. Serum COX inhibition was evaluated in vitro and ex vivo in untreated elephant plasma, where firocoxib demonstrated preferential inhibition of COX-2. No adverse effects from firocoxib administration were identified in this study. Results suggest administering firocoxib to Asian elephants at a dose of 0.1 mg/kg orally, using either tablet or paste formulations, every 24 h.


Assuntos
4-Butirolactona/análogos & derivados , Elefantes , Sulfonas , Animais , Ciclo-Oxigenase 2 , Monitoramento de Medicamentos , Administração Oral , Anti-Inflamatórios não Esteroides , Comprimidos , Área Sob a Curva , Estudos Cross-Over , Meia-Vida
2.
J Zoo Wildl Med ; 54(2): 350-359, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37428699

RESUMO

The time course of serum firocoxib concentrations was described after administration of two single oral doses (0.01 and 0.1 mg/kg) of commercially available firocoxib tablet (n = 4) and paste (n = 2) formulations to six healthy adult female African (Loxodonta africana) elephants. Firocoxib was quantitated by high-performance liquid chromatography. Firocoxib serum concentrations were below detectable levels after administration of 0.01 mg/kg of both formulations. A dose of 0.1 mg/kg (n = 4) of the tablet formulation had the following mean ± SD of pharmacokinetic parameters: area under the curve (AUC) 1,588 ± 362 h × ng/ml, maximum plasma concentration (Cmax) 31 ± 6.6 ng/ml at 6.4 ± 1.8 h, and disappearance half-life (T1/2) 66 ± 59 h, Elephant compliance to oral administration of the paste formulation was challenging, with only two elephants accepting administration of the paste at 0.1 mg/kg. Pharmacokinetic parameters determined included AUC of 814 h × ng/ml, Cmax of 44 ng/ml at Tmax of 7.0 h, and T1/2 of 36.4 h. Based on mean AUC, the relative bioavailability of paste compared to tablet formulations was 50%. Limitations of this study were the small number of participants and elephant compliance with the paste formulation. This study supports an oral dose of 0.1 mg/kg every 24 h. Multidose and IV trials are indicated to confirm firocoxib dosing requirements for African elephants.


Assuntos
Elefantes , Feminino , Animais , Sulfonas/farmacocinética , 4-Butirolactona/farmacocinética , Administração Oral , Área Sob a Curva , Comprimidos , Estudos Cross-Over
3.
J Zoo Wildl Med ; 51(4): 905-914, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33480571

RESUMO

Flunixin meglumine is the most commonly used nonsteroidal anti-inflammatory drug used to treat elephants; however, no pharmacokinetic study for flunixin has yet been conducted in these species, and dosages used range widely. Pharmacokinetic parameters of flunixin were determined in African (Loxodonta africana) and Asian (Elephas maximus) elephants after single-dose oral administration of 0.8 and 1.5 mg/kg flunixin paste in each species. Elephant compliance to oral administration of banamine was occasionally challenging, especially among older, female African elephants. After administration of 0.8 mg/kg flunixin, mean serum concentrations peaked in approximately 1.3 hr at 2.1 ± 0.8 µg/ml for Asian (n = 8) and 2.8 hr at 2.5 ± 0.7 µg/ml for African (n = 8) elephants. Dosages of 1.5 mg/kg flunixin resulted in mean serum concentration peaks of 7.2 ± 1.5 µg/ml in Asian elephants (n = 7) and 4.4 ± 0.7 µg/ml in African elephants (n = 6). However, multiple-dose trials using 1.1 mg/kg flunixin resulted in peak serum concentrations that were again less in Asian than African elephants (2.7 µg/ml versus 4.4 µg/ml, respectively). Asian elephants consistently had lower time to maximal concentration, greater area under the curve, and longer mean residence times compared with African elephants. In other species, flunixin is excreted unchanged primarily via hepatic routes with small amounts in the urine. Asian elephants may engage in some level of enterohepatic recycling of flunixin, as was previously reported for phenylbutazone. This study supports that different oral dosing regimens should be used for Asian (1.0 mg/kg SID) and African (1.2 mg/kg SID) elephants, and oral administration techniques used should ensure complete dosage delivery.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Clonixina/análogos & derivados , Elefantes/metabolismo , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/sangue , Área Sob a Curva , Clonixina/administração & dosagem , Clonixina/sangue , Clonixina/farmacocinética , Feminino , Meia-Vida , Masculino , Projetos Piloto
4.
Pharm Dev Technol ; 19(1): 10-20, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23259589

RESUMO

A promising glipizide formulation comprising compression of four-layer coated beads into tablets was prepared. The tablet offered the advantages of: a two-hour lag time before drug release, retaining sustained release characteristics and providing approximately zero-order drug release. Drug release was nearly independent of paddle speeds of 50 and 100 rpm releasing 80% over 14 h similar to the commercial glipizide osmotic pump tablet during dissolution testing while keeping the benefits of multiparticular dosage forms. The tablets contain beads with four layers: (1) the innermost layer consists of 2.5 g glipizide and 3.75 g solid ethylcellulose (Surelease®) coated onto 71.25 g of sugar beads; (2) next a hardening layer of 5 g of hypromellose; (3) the controlled release layer of 7.5 g of Surelease®:lactose at a solids ratio of 100:7 and (4) an outermost layer of 20 g of lactose:sodium starch glycolate (Explotab®) at a 2:1 ratio. Then, beads were compressed into tablets containing 11 mg of glipizide using 1500 lbs of compression pressure. The dissolution test similarity factor (f2) was above 50 for all test conditions for formulation F13 and Glucotrol® with a high of 69.9. The two Surelease® layers both aid controlling drug release, with the Surelease®-drug layer affecting drug release to a greater extent.


Assuntos
Preparações de Ação Retardada/química , Glipizida/administração & dosagem , Hipoglicemiantes/administração & dosagem , Celulose/análogos & derivados , Celulose/química , Composição de Medicamentos , Derivados da Hipromelose , Lactose/química , Metilcelulose/análogos & derivados , Metilcelulose/química , Solubilidade , Amido/análogos & derivados , Amido/química , Comprimidos
5.
Pharmacol Res ; 66(3): 199-206, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22609537

RESUMO

Lipoic acid (LA) shows promise as a beneficial micronutrient toward improving elder health. Studies using old rats show that (R)-α-LA (R-LA) significantly increases low molecular weight antioxidants that otherwise decline with age. Despite this rationale for benefiting human health, little is known about age-associated alterations in absorption characteristics of LA, or whether the commercially available racemic mixture of LA (R,S-LA) is equally as bioavailable as the naturally occurring R-enantiomer. To address these discrepancies, a pilot study was performed to establish which form of LA is most effectively absorbed in older subjects relative to young volunteers. Young adults (average age=32 years) and older adults (average age=79 years) each received 500 mg of either R- or R,S-LA. Blood samples were collected for 3h after supplementation. After a washout period they were given the other chiral form of LA not originally ingested. Results showed that 2 out of 6 elder males exhibited greater maximal plasma LA and area under the curve for the R-form of LA versus the racemic mixture. The elder subjects also demonstrated a reduced time to reach maximal plasma LA concentration following R-LA supplementation than for the racemic mixture. In contrast, young males had a tendency for increased bioavailability of R,S-LA. Overall, bioavailability for either LA isoform was much more variable between older subjects compared to young adults. Plasma glutathione levels were not altered during the sampling period. Thus subject age, and potential for varied response, should be considered when determining an LA supplementation regimen.


Assuntos
Ácido Tióctico/farmacocinética , Adulto , Fatores Etários , Idoso , Antioxidantes/metabolismo , Disponibilidade Biológica , Suplementos Nutricionais , Feminino , Glutationa/metabolismo , Humanos , Masculino , Projetos Piloto , Fatores Sexuais , Estereoisomerismo , Ácido Tióctico/sangue , Ácido Tióctico/química , Ácido Tióctico/farmacologia
6.
Pharm Dev Technol ; 17(1): 73-83, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-20923254

RESUMO

Novel 'beads-in-a-tablet' formulations (total weight ∼740-780 mg) have been prepared that meet USP 31 requirements for Delayed Release of mesalamine. Several methods are presented that overcome breakage of beads during tablet compaction were explored. Bead formulations comprise a combination of extrusion and spheronization to produce a relatively high drug load (80%), followed by coating (25%) with a colonic-targeted drug release polymer (polymethacrylates, Eudragit(®) S100), overcoated (3%) with hydroxypropyl methylcellulose (Opadry(®)) to improve bead binding and compactability, and using 20% coat of lactose/sodium starch glycolate (Explotab(®)) as binder/disintegrant/cushioning agent, thus allowing a sufficiently thick coating to be uniform and without being broken during tablet compaction. Then, the aforementioned beads were compressed into tablets at 1500 pounds of pressure containing 400 mg of mesalamine, and finally coating the compressed tablets with Surelease(®) (ethylcellulose):Opadry(®) = 1:0.5 ranging from 1.5-2.5% weight gain; the resulting tablets met USP 31 dissolution requirements for delayed release tablets.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Colo , Sistemas de Liberação de Medicamentos , Mesalamina/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Celulose/análogos & derivados , Química Farmacêutica , Preparações de Ação Retardada , Composição de Medicamentos , Excipientes , Mesalamina/química , Ácidos Polimetacrílicos , Polivinil , Solubilidade , Comprimidos
7.
Pharm Dev Technol ; 17(2): 148-57, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-20958129

RESUMO

A novel bead formulation of verapamil hydrochloride was developed comprising a combination of extrusion and spheronization to produce a relatively high drug load, followed by coating of the bead with an insoluble polymer (ethylcellulose) that contains a water soluble channeling agent (lactose), thus allowing the application of a sufficiently thick outer coating that is uniform and robust without 'shutting down' release of the relatively insoluble drug. The new formulation provided the unexpected benefit that by adjusting both coating thickness and ethylcellulose/lactose ratio, it is possible to obtain essentially non-agitation sensitive and approximately zero-order drug release up to 14 hours in either KCl or two pH media, at stirring speeds of either 75 or 200 rpm with either the USP basket or USP paddle stirring method.


Assuntos
Antiarrítmicos/administração & dosagem , Celulose/análogos & derivados , Preparações de Ação Retardada/química , Lactose/química , Verapamil/administração & dosagem , Celulose/química , Cinética , Solubilidade
8.
Am J Vet Res ; 82(10): 811-817, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34554869

RESUMO

OBJECTIVE: To investigate associations between short-term treatment with a previously described compounded transdermal formulation of atenolol and heart rate in cats. ANIMALS: 11 healthy adult cats. PROCEDURES: Cats received the atenolol gel formulation (gradually increased from 12.5 mg/cat, q 24 h to 25 mg/cat, q 12 h) by application to the pinnae at home over a 10-day period in a prospective, experimental study. On day 10, cats were hospitalized for measurement of serum atenolol concentrations 3, 6, and 12 hours after the morning treatment. Mean heart rate measured at the 3- and 6-hour time points was compared with a baseline value (measured at enrollment). RESULTS: All cats completed the study; 4 were excluded from analyses after an apparent formulation error was detected in 1 batch. Two cats had minor adverse effects (localized erythema of the pinna). Five of 7 cats had serum atenolol concentrations ≥ 260 ng/mL (considered therapeutic) at ≥ 1 time point. Heart rate had a strong negative correlation (r = -0.87) with serum atenolol concentration. A 90-day drug stability investigation of 4 formulations (identical to the intended study treatment except for pH [range, 6.5 to 7.7]) revealed an apparent decrease in atenolol concentration at a pH of 7.7. CONCLUSIONS AND CLINICAL RELEVANCE: Topical administration of the formulation as described resulted in targeted serum atenolol concentrations in most cats, with attendant HR reduction. Validation of these preliminary results in a larger sample and investigation of the treatment in cats with structural heart disease is needed. Verification of appropriate pH (target, 7.0) is likely essential for the compound's stability.


Assuntos
Atenolol , Administração Cutânea , Animais , Frequência Cardíaca , Estudos Prospectivos
9.
Drug Dev Ind Pharm ; 36(4): 393-404, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19740039

RESUMO

BACKGROUND: The basic objective of this study was to develop a novel technique that aids in compaction of coated pellets into tablets and obtain a release pattern from compressed pellets resembling the same pattern before compression. METHOD: Multi-unit dosage forms of mesalamine targeted to the colon were formulated by extrusion-spheronization, and then coated with Eudragit S (30%). These pellets were filled into gelatin capsules or further formulated and compressed into tablets. Tablets for colonic delivery of mesalamine were prepared by mixing the coated beads with cushioning agents like stearic acid and Explotab, or by applying an additional coat of gelatin (4% weight gain) onto the Eudragit S coated pellets, and then compressing into tablets (tableted reservoir-type pellets). Then additional coating of the tablets prepared by the coating technique was applied utilizing Eudragit L 100-55 (5% weight gain). RESULTS: This technique provides additive protection for the coated beads to withstand the compression force during tableting. Excellent in vitro dissolution results were obtained, which were comparable to the results of the release of mesalamine from uncompressed beads filled in capsules. Mesalamine release from the capsules was 0.3% after 2 hours in gastric pH, 0.37% was released after an additional 1 hour in pH 6, and 89% was released after 1.5 hours in colonic pH 7.2. CONCLUSION: Various formulation and process parameters have to be optimized in order to obtain tableted reservoir-type pellets having the same release properties as the uncompressed pellets. The coating technique delays the release of mesalamine until the beads reach the terminal ileum and colon. Once released in the colon, mesalamine is minimally absorbed and can act locally to treat ulcerative colitis.


Assuntos
Implantes de Medicamento/análise , Excipientes/química , Mesalamina/administração & dosagem , Mesalamina/química , Administração Oral , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Química Farmacêutica , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Mesalamina/farmacocinética , Ácidos Polimetacrílicos , Comprimidos/análise
10.
J Zoo Wildl Med ; 41(2): 263-74, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20597218

RESUMO

The objective of this study was to determine the pharmacokinetic parameters of orally administered terbinafine hydrochloride based on 3, 7, and 15 mg/kg single- as well as multiple-dosage trials in order to calculate dosing requirements for potential treatment of aspergillosis in African penguins (Spheniscus demersus). Ten adult African penguins were used in each of these trials, with a 2-wk washout period between trials. Mean plasma concentrations of terbinafine peaked in approximately 4 hrs at 0.11 +/- 0.017 microg/ml (mean +/- SD) following administration of 3 mg/kg terbinafine, while 7 mg/kg and 15 mg/kg dosages resulted in peak plasma concentrations of 0.37 +/- 0.105 and 0.33 +/- 0.054 microg/ml, respectively. The volume of distribution increased with increasing dosages, being 37 +/- 28.5, 40 +/- 28.1, and 52 +/- 18.6 mg/L for 3, 7, and 15 mg/kg doses, respectively. The mean half-life was biphasic with initial terminal half-life (t(1/2)) values of 9.9 +/- 4.5, 17.2 +/- 4.9 and 16.9 +/- 5.4 hrs, for 3, 7, and 15 mg/kg doses, respectively. A rapid first elimination phase was followed by a slower second phase, and final elimination was estimated to be 136 +/- 9.7 and 131 +/- 9.9 hrs, for 7 and 15 mg/kg doses, respectively. Linearity was demonstrated for area under the curve but not for peak plasma concentrations for the three dosages used. Calculations based on pharmacokinetic parameter values indicate that a 15 mg/kg terbinafine q24h dosage regimen would result in steady-state trough plasma concentrations above the minimum inhibitory concentration (0.8-1.6 microg/ ml), and this dosage is recommended as a potential treatment option for aspergillosis in penguins. However, additional research is required to determine both treatment efficacy and safety.


Assuntos
Antifúngicos/farmacocinética , Aspergilose/veterinária , Doenças das Aves/tratamento farmacológico , Naftalenos/farmacocinética , Spheniscidae , Animais , Antifúngicos/sangue , Antifúngicos/química , Antifúngicos/uso terapêutico , Área Sob a Curva , Aspergilose/tratamento farmacológico , Relação Dose-Resposta a Droga , Feminino , Meia-Vida , Masculino , Estrutura Molecular , Naftalenos/sangue , Naftalenos/química , Naftalenos/uso terapêutico , Terbinafina
11.
J Avian Med Surg ; 24(2): 122-30, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20806657

RESUMO

To determine pharmacokinetic parameters of orally administered terbinafine hydrochloride for potential treatment of aspergillosis in raptors, 10 adult red-tailed hawks (Buteo jamaicensis) were used in single dose trials by using 15, 30, and 60 mg/kg doses with a 2-week washout period between trials. After administration of 15 mg/kg terbinafine, mean (+/- SD) plasma concentration peaked in approximately 5 hours at 0.3 +/- 0.24 microg/mL, whereas a 30 mg/kg dose resulted in peak mean (+/- SD) plasma concentration of 1.2 +/- 0.40 microg/mL in 3 hours and a 60 mg/kg dose resulted in mean (+/- SD) concentration of 2.0 +/- 0.75 microg/mL in 5 hours. The volume of distribution decreased with increasing doses, averaging 76.8 +/- 38.06 mL/kg for the 15 mg/kg dose and falling to 55.2 +/- 17.4 mL/kg for the 30 mg/kg dose. This suggests that terbinafine accumulated in deep tissues, limiting further distribution at higher doses. The harmonic mean (+/- SD) half-life was biphasic, with initial values of 14.7 +/- 6.67 hours, 17.5 +/- 8.7 hours, and 13.3 +/- 5.03 hours for 15, 30, and 60 mg/kg doses, respectively. A rapid first-elimination phase was followed by a slower second phase, and final elimination was estimated to be 161 +/- 78.2 and 147 +/- 65.6 hours for 15 and 30 mg/kg doses, respectively. Linearity was demonstrated for the area under the curve but not for peak plasma concentrations for the 3 doses used. Calculations based on pharmacokinetic parameter values indicated that a dosage of 22 mg/kg terbinafine q24h would result in steady-state trough plasma concentrations above the minimum inhibitory concentration of terbinafine (0.8-1.6 microg/mL). This dosage is recommended as a potential treatment option for aspergillosis in raptors. However, additional research is required to determine both treatment efficacy and safety.


Assuntos
Antifúngicos/farmacocinética , Naftalenos/farmacocinética , Aves Predatórias/metabolismo , Administração Oral , Animais , Antifúngicos/administração & dosagem , Antifúngicos/sangue , Área Sob a Curva , Relação Dose-Resposta a Droga , Meia-Vida , Fígado/metabolismo , Pulmão/metabolismo , Músculo Esquelético/metabolismo , Naftalenos/administração & dosagem , Naftalenos/sangue , Terbinafina , Distribuição Tecidual
12.
Drug Dev Ind Pharm ; 35(8): 1009-21, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19274589

RESUMO

Nifedipine release from coated commercially available immediate release soft elastic gelatin capsules was investigated. Capsules were spray coated using two different polymeric combinations, ethylcellulose and hydroxypropylmethylcellulose or pectin, at different coating loads. In vitro drug release studies were conducted in three different dissolution media: with gastric pretreatment, without gastric pretreatment, and in water to investigate the pH effect on nifedipine release. Convolution of in vitro dissolution data for selected formulations and commercially available sustained release nifedipine formulations showed that the tested formulations provided release profiles of nifedipine that are very promising in terms of desirable sustained release formulations.


Assuntos
Bloqueadores dos Canais de Cálcio/administração & dosagem , Excipientes/química , Nifedipino/administração & dosagem , Bloqueadores dos Canais de Cálcio/química , Cápsulas , Celulose/análogos & derivados , Celulose/química , Preparações de Ação Retardada , Gelatina , Concentração de Íons de Hidrogênio , Derivados da Hipromelose , Metilcelulose/análogos & derivados , Metilcelulose/química , Nifedipino/química , Pectinas/química , Polímeros/química , Solubilidade
13.
Pharm Dev Technol ; 14(1): 116-25, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-18821272

RESUMO

The goal was to use temporal gastrointestinal transit simulations and formulation to predict and provide sustained input of target-site directed oral drug delivery exclusively into the colon. Using mesalamine as the model drug for formulation coupled with stomach emptying rates (fed and unfed) plus intestinal transit times demonstrates concepts and provides a specific example for treatment in ulcerative colitis. Formulation involved extrusion and spheronization into beads which were then coated with aqueous Eudragit S. Drug is released only at colonic pH and gastrointestinal transit predicts sustained drug input into the colon, especially when food effects are included.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Química Farmacêutica , Colo/efeitos dos fármacos , Preparações de Ação Retardada/farmacocinética , Trânsito Gastrointestinal/efeitos dos fármacos , Mesalamina/farmacocinética , Absorção/efeitos dos fármacos , Administração Oral , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/metabolismo , Disponibilidade Biológica , Colo/metabolismo , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/metabolismo , Formas de Dosagem , Alimentos , Trânsito Gastrointestinal/fisiologia , Humanos , Absorção Intestinal , Mesalamina/administração & dosagem , Mesalamina/metabolismo , Farmacocinética , Farmacopeias como Assunto , Ácidos Polimetacrílicos/química , Solubilidade , Tecnologia Farmacêutica , Fatores de Tempo
14.
JPEN J Parenter Enteral Nutr ; 43(3): 426-433, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30156306

RESUMO

BACKGROUND: Parenteral nutrition (PN) solutions containing calcium gluconate (CaGlu) and cysteine have elevated particle counts when analyzed using laser light obscuration (LO) as recommended by the United States Pharmacopeia (USP). There are no compatibility studies for solutions compounded with cysteine and containing calcium chloride (CaCl2 ) using LO. The purpose of this study was to conduct compatibility testing for neonatal PN solutions containing CaCl2 and CaGlu with cysteine. METHODS: Solutions of amino acids (2.5%), containing either CaCl2 or CaGlu plus potassium phosphate, were compounded with 50 and 100 mg/dL cysteine. Solutions were analyzed for particle counts using LO. Maximum concentrations tested were 20 mmol/L calcium and 15 mmol/L phosphate. Three solutions containing CaCl2 (144 total solutions) and 2 containing CaGlu (96 total solutions) and the same concentration of additives were compounded. If the average particle count of replicates exceeded USP guidelines, the solution was incompatible. RESULTS: All solutions containing CaGlu had particle counts that exceeded USP guidelines for particle counts ≥10 µm (range, 86-580 particles/mL). For CaCl2 , 90 of 144 solutions were compatible (range of particle counts for all solutions, 3-121 particles/mL). Maximum compatible concentrations of CaCl2 and potassium phosphate were 15 mmol/L and 12.5 mmol/L, respectively, for solutions containing both 50 and 100 mg/dL cysteine. CONCLUSION: This study found that neonatal PN solutions containing CaGlu with added cysteine have significantly higher particle counts, exceeding USP guidelines for compatibility, than those containing CaCl2 .


Assuntos
Cloreto de Cálcio/química , Gluconato de Cálcio/química , Cisteína/química , Difusão Dinâmica da Luz/métodos , Soluções de Nutrição Parenteral/análise , Soluções de Nutrição Parenteral/química , Precipitação Química , Composição de Medicamentos/métodos , Humanos , Recém-Nascido
15.
J Antimicrob Chemother ; 62(4): 769-72, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18593725

RESUMO

OBJECTIVES: Community-associated methicillin-resistant Staphylococcus aureus is responsible for an increasing number of skin infections. Over-the-counter topical wound care products may play a role in the prevention of these infections, but limited data are available regarding their activity. The current study utilized a modified time-kill design to evaluate the activity of three over-the-counter topical wound care products (benzethonium chloride/essential oils, neomycin/polymyxin B and polymyxin B/gramicidin) against four unique isolates (three USA 300 and one USA 400). METHODS: All experiments were performed using commercially available formulations. Bactericidal activity was defined as a sustained 3 log(10) reduction in cfu/mL from the initial inoculum. Reductions in bacterial counts between agents were determined using analysis of variance. RESULTS: At 10 min, the reduction (mean +/- SD) in log(10) cfu/mL for all strains was 2.87 +/- 1.22, 1.86 +/- 0.76 and 0.143 +/- 0.82 for benzethonium chloride/essential oils, neomycin/polymyxin B and polymyxin B/gramicidin, respectively. By 24 h, bactericidal activity was observed against two strains each for neomycin/polymyxin B and polymyxin B/gramicidin. Benzethonium chloride/essential oils was bactericidal against all strains by 6 h. At 24 h, all three agents were superior to controls (P < 0.05). Benzethonium chloride/essential oils was more active at 24 h than polymyxin B/gramicidin versus all four strains (P < 0.05) and more active than neomycin/polymyxin B versus three of four strains (P < 0.05). CONCLUSIONS: These topical agents demonstrated variable activity against the four strains tested. Benzethonium chloride/essential oils was more rapidly and completely active than the other agents tested.


Assuntos
Antibacterianos/farmacologia , Anti-Infecciosos Locais/farmacologia , Infecções Comunitárias Adquiridas/microbiologia , Resistência a Meticilina , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Contagem de Colônia Microbiana , Viabilidade Microbiana , Staphylococcus aureus/isolamento & purificação , Fatores de Tempo
16.
J Zoo Wildl Med ; 39(2): 188-200, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18634209

RESUMO

The pharmacokinetic parameters of phenylbutazone were determined in 18 elephants (Loxodonta africana and Elephas maximus) after single-dose oral administration of 2, 3, and 4 mg/kg phenylbutazone, as well as multiple-dose administrations with a 4-wk washout period between trials. After administration of 2 mg/kg phenylbutazone, mean serum concentrations peaked in approximately 7.5 hr at 4.3 +/- 2.02 microg/ml and 9.7 hr at 7.1 +/- 2.36 microg/ml for African and Asian elephants, respectively, while 3 mg/kg dosages resulted in peak serum concentrations of 7.2 +/- 4.06 microg/ml in 8.4 hr and 12.1 +/- 3.13 microg/ml in 14 hr. The harmonic mean half-life was long, ranging between 13 and 15 hr and 39 and 45 hr for African and Asian elephants, respectively. There was evidence of enterohepatic cycling of phenylbutazone in Asian elephants. Significant differences (P < 0.0001) in pharmacokinetic values occurred between African and Asian elephants for clearance (27.9 and 7.6 ml/hr/kg, respectively), terminal half-life (15.0 and 38.7 hr, respectively), and mean residence time (22.5 and 55.5 hr, respectively) using 2-mg/kg dosages as an example. This suggests that different treatment regimens for Asian and African elephants should be used. There were no apparent gender differences in these parameters for either elephant species.


Assuntos
Elefantes/metabolismo , Fenilbutazona/farmacocinética , Administração Oral , Animais , Animais de Zoológico/metabolismo , Área Sob a Curva , Estudos Cross-Over , Relação Dose-Resposta a Droga , Feminino , Meia-Vida , Masculino , Fenilbutazona/administração & dosagem , Distribuição Aleatória , Especificidade da Espécie
17.
Mol Nutr Food Res ; 62(6): e1700692, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29322620

RESUMO

SCOPE: Xanthohumol (XN), a prenylated flavonoid found in hops, exhibits anti-inflammatory and antioxidant properties. However, poor bioavailability may limit therapeutic applications. As food components are known to modulate polyphenol absorption, the objective is to determine whether a protein matrix could enhance the bioavailability of XN post oral consumption in humans. METHODS AND RESULTS: This is a randomized, double-blind, crossover study in healthy participants (n = 6) evaluating XN and its major metabolites (isoxanthohumol [IX], 6- and 8-prenylnaringenin [6-PN, 8-PN]) for 6 h following consumption of 12.4 mg of XN delivered via a spent hops-rice protein matrix preparation or a control spent hops preparation. Plasma XN and metabolites are measured by LC-MS/MS. Cmax , Tmax , and area-under-the-curve (AUC) values were determined. Circulating XN and metabolite response to each treatment was not bioequivalent. Plasma concentrations of XN and XN + metabolites (AUC) are greater with consumption of the spent hops-rice protein matrix preparation. CONCLUSION: Compared to a standard spent hops powder, a protein-rich spent hops matrix demonstrates enhanced plasma levels of XN and metabolites following acute oral intake.


Assuntos
Flavonoides/sangue , Humulus , Oryza/química , Proteínas de Vegetais Comestíveis/administração & dosagem , Propiofenonas/sangue , Administração Oral , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino
18.
Nutrients ; 10(2)2018 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-29443921

RESUMO

There are no compatibility studies for neonatal parenteral nutrition solutions without cysteine containing calcium chloride or calcium gluconate using light obscuration as recommended by the United States Pharmacopeia (USP). The purpose of this study was to do compatibility testing for solutions containing calcium chloride and calcium gluconate without cysteine. Solutions of TrophAmine and Premasol (2.5% amino acids), containing calcium chloride or calcium gluconate were compounded without cysteine. Solutions were analyzed for particle counts using light obscuration. Maximum concentrations tested were 15 mmol/L of calcium and 12.5 mmol/L of phosphate. If the average particle count of three replicates exceeded USP guidelines, the solution was determined to be incompatible. This study found that 12.5 and 10 mmol/L of calcium and phosphate, respectively, are compatible in neonatal parenteral nutrition solutions compounded with 2.5% amino acids of either TrophAmine or Premasol. There did not appear to be significant differences in compatibility for solutions containing TrophAmine or Premasol when solutions were compounded with either CaCl2 or CaGlu-Pl. This study presents data in order to evaluate options for adding calcium and phosphate to neonatal parenteral nutrition solutions during shortages of calcium and cysteine.


Assuntos
Cloreto de Cálcio/análise , Gluconato de Cálcio/análise , Composição de Medicamentos , Incompatibilidade de Medicamentos , Fenômenos Fisiológicos da Nutrição do Lactente , Soluções de Nutrição Parenteral/química , Aminoácidos/química , Aminoácidos/normas , Difusão Dinâmica da Luz , Eletrólitos/química , Eletrólitos/normas , Glucose/química , Glucose/normas , Humanos , Concentração de Íons de Hidrogênio , Recém-Nascido , Lasers , Concentração Osmolar , Soluções de Nutrição Parenteral/normas , Farmacopeias como Assunto , Fosfatos/química , Compostos de Potássio/química , Soluções/química , Soluções/normas , Estados Unidos
19.
J Zoo Wildl Med ; 38(2): 258-68, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17679510

RESUMO

The pharmacokinetic parameters of S(+) and R(-) ibuprofen were determined in 20 elephants after oral administration of preliminary 4-, 5-, and 6-mg/kg doses of racemic ibuprofen. Following administration of 4 mg/kg ibuprofen, serum concentrations of ibuprofen peaked at 5 hr at 3.9 +/- 2.07 microg/ml R(-) and 10.65 +/- 5.64 microg/ml S(+) (mean +/- SD) in African elephants (Loxodonta africana) and at 3 hr at 5.14 +/- 1.39 microg/ml R(-) and 13.77 +/- 3.75 microg/ml S(+) in Asian elephants (Elephas maximus), respectively. Six-milligram/kilogram dosages resulted in peak serum concentrations of 5.91 +/- 2.17 microg/ml R(-) and 14.82 +/- 9.71 microg/ml S(+) in African elephants, and 5.72 +/- 1.60 microg/ml R(-) and 18.32 +/- 10.35 microg/ml S(+) in Asian elephants. Ibuprofen was eliminated with first-order kinetics characteristic of a single-compartment model with a half-life of 2.2-2.4 hr R(-) and 4.5-5.1 hr S(+) in African elephants and 2.4-2.9 hr R(-) and 5.9-7.7 hr S(+) in Asian elephants. Serum concentrations of R(-) ibuprofen were undetectable at 24 hr, whereas S(+) ibuprofen decreased to below 5 microg/ml 24 hr postadministration in all elephants. The volume of distribution was estimated to be between 322 and 356 ml/kg R(-) and 133 and 173 ml/kg S(+) in Asian elephants and 360-431 ml/kg R(-) and 179-207 ml/kg S(+) in African elephants. Steady-state serum concentrations of ibuprofen ranged from 2.2 to 10.5 microg/ml R(-) and 5.5 to 32.0 microg/ml S(+) (mean: 5.17 +/- 0.7 R(-) and 13.95 +/- 0.9 S(+) microg/ml in African elephants and 5.0 +/- 1.09 microg/ml R(-) and 14.1 +/- 2.8 microg/ml S(+) in Asian elephants). Racemic ibuprofen administered at 6 mg/kg/12 hr for Asian elephants and at 7 mg/kg/12 hr for African elephants results in therapeutic serum concentrations of this antiinflammatory agent.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Peso Corporal/fisiologia , Elefantes/metabolismo , Ibuprofeno/farmacocinética , Administração Oral , Animais , Animais de Zoológico , Área Sob a Curva , Feminino , Meia-Vida , Isomerismo , Masculino , Especificidade da Espécie
20.
Nutr Clin Pract ; 32(2): 266-270, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29927528

RESUMO

INTRODUCTION: Calcium chloride (CaCl2 ) has been the only calcium additive available in the United States that has a low aluminum (Al) content. Calcium gluconate in glass vials (CaGluc-Gl) has a high Al content while calcium gluconate in plastic vials (CaGluc-Pl) has a low Al content. The purpose of this study was to measure Al concentrations in neonatal parenteral nutrition (PN) solutions prepared using various calcium additives. METHODS: Samples of solutions compounded with CaCl2 or CaGluc-Gl and sodium phosphate (NaPhos) as well as CaGluc-Pl and sodium glycerophosphate (NaGP) with and without cysteine were analyzed for Al content. Samples of the cysteine and calcium gluconate additives were also sent for analysis. RESULTS: Solutions containing CaCl2 and CaGlu-Pl had mean Al concentrations of 1.2-2.3 mcg/dL, while those with CaGlu-Gl had mean concentrations of 14.6-15.1 mcg/dL. Solutions made with NaGP were low in Al content. The measured Al content of 2 lots of the cysteine additive were 168 ± 23 mcg/L and 126 ± 5 mcg/L. The Al concentration equalled 2730 ± 20 mcg/L for the CaGlu-Gl additive and 310 ± 80 mcg/L for the CaGlu-Pl additive. CONCLUSION: The study indicates that solutions containing CaCl2 or CaGluc-Pl and NaPhos or NaGP are low in Al content. Using these options for calcium and phosphate additives can limit aluminum intake from neonatal PN to levels within the Food and Drug Administration guideline of ≤5 mcg/kg/d.


Assuntos
Alumínio/análise , Soluções de Nutrição Parenteral/química , Alumínio/administração & dosagem , Cloreto de Cálcio/química , Gluconato de Cálcio/química , Cisteína/química , Glicerofosfatos/química , Humanos , Recém-Nascido , Soluções de Nutrição Parenteral/efeitos adversos , Fosfatos/química , Estados Unidos
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