RESUMO
Angiogenesis facilitates the formation of microvascular networks and promotes neurological deficit recovery after cerebral ischemia-reperfusion injury (CIRI). This study investigated the angiogenesis effects of 4-methoxy benzyl alcohol (4-MA) on CIRI. The angiogenesis effects of 4-MA and the potential underlying mechanisms were assessed based on a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model and a hind limb ischemic (HLI) mouse model. Immunofluorescence was conducted to detect microvessel density, and Western blotting and polymerase chain reaction were performed to determine the expression of angiogenesis-promoting factors. In addition, we investigated whether the angiogenesis effects of 4-MA caused damage to the blood-brain barrier (BBB). After treatment with 4-MA (20 mg/kg) for 7 days, the neurological deficits recovered and microvessel density in the cerebral cortex increased in the MCAO/R rats. Additionally, 4-MA also regulated the expression of angiogenesis factors, with an increase in vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR-2) expression and a decrease in angiopoietin 1 (Ang-1), Ang-2, and Tie-2 expression in both MCAO/R rats and HLI mice. Moreover, 4-MA increased the expression of angiogenesis-promoting factors without exacerbating BBB cascade damage in MCAO/R rats. Our results indicated that 4-MA may contribute to the formation of microvascular networks, thus promoting neurological deficit recovery after CIRI.
Assuntos
Indutores da Angiogênese , Álcool Benzílico/administração & dosagem , Álcool Benzílico/farmacologia , Isquemia Encefálica/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Angiopoietina-1/genética , Angiopoietina-1/metabolismo , Angiopoietina-2/genética , Angiopoietina-2/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Masculino , Camundongos , Ratos Sprague-Dawley , Receptor TIE-2/genética , Receptor TIE-2/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
Benzyl alcohol is an excipient used in many drugs as a stabilizer. Depending on the amount present in drug formulations there might be confounding findings in the Abnormal Toxicity Test (ATT). The ATT is utilized as a quality control (QC) release test to detect extraneous contaminants according to national pharmacopoeias. Our study assessed the effects of benzyl alcohol as defined in ATT designs. This study - the first thorough evaluation of the confounding effects of benzyl alcohol on the ATT - was conducted in relation to particular health authority questions and was part of the root-cause analyses resulting from some transient behavioral findings observed in the test. Two strains of mice, CD-1 & Kunming, plus Hartley guinea pigs were administered intraperitoneally (ip), subcutaneously (sc), or intravenously (iv) with benzyl alcohol at dose level defined in the ATT design. In both mice and guinea pigs, only after ip administration, minimal behavioral changes were observed transiently within 2-3 min after administration. Therefore, the presence of benzyl alcohol in the product batch may confound the ATT results. This study provides further evidence to question the validity of the ATT for its intended use.
Assuntos
Álcool Benzílico/toxicidade , Excipientes/toxicidade , Farmacopeias como Assunto , Testes de Toxicidade/métodos , Animais , Álcool Benzílico/administração & dosagem , Álcool Benzílico/química , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Química Farmacêutica , Excipientes/administração & dosagem , Excipientes/química , Feminino , Cobaias , Masculino , Camundongos , Mortalidade/tendênciasRESUMO
OBJECTIVE: To compare the pharmacokinetics and pharmacodynamics of propofol with or without 2% benzyl alcohol administered intravenously (IV) as a single induction dose in cats. STUDY DESIGN: Prospective experimental study. ANIMALS: Six healthy adult cats, three female intact, three male castrated, weighing 4.8 ± 1.8 kg. METHODS: Cats received 8 mg kg(-1) IV of propofol (P) or propofol with 2% benzyl alcohol (P28) using a randomized crossover design. Venous blood samples were collected at predetermined time points to 24 hours after drug administration to determine drug plasma concentrations. Physiologic and behavioral variables were also recorded. Propofol and benzyl alcohol concentrations were determined using high pressure liquid chromatography with fluorescence detection. Pharmacokinetic parameters were described using a 2-compartment model. Pharmacokinetic and pharmacodynamic parameters were analyzed using repeated measures anova (p < 0.05). RESULTS: Plasma concentrations of benzyl alcohol were below the lower limits of quantification (LLOQ) at all time points for two of the six cats (33%), and by 30 minutes for the remaining four cats. Propofol pharmacokinetics, with or without 2% benzyl alcohol, were characterized by rapid distribution, a long elimination phase, and a large volume of distribution. No differences were noted between treatments with the exception of clearance from the second compartment (CLD2), which was 23.6 and 38.8 mL kg(-1) minute(-1) in the P and P28 treatments, respectively. Physiologic and behavioral variables were not different between treatments with the exception of heart rate at 4 hours post administration. CONCLUSIONS AND CLINICAL RELEVANCE: The addition of 2% benzyl alcohol as a preservative minimally altered the pharmacokinetics and pharmacodynamics of propofol 1% emulsion when administered as a single IV bolus in this group of cats. These data support the cautious use of propofol with 2% benzyl alcohol for induction of anesthesia in healthy cats.
Assuntos
Anestésicos Intravenosos/farmacologia , Álcool Benzílico/administração & dosagem , Gatos/fisiologia , Propofol/farmacologia , Período de Recuperação da Anestesia , Anestesia Intravenosa/veterinária , Anestésicos Intravenosos/sangue , Anestésicos Intravenosos/farmacocinética , Animais , Gatos/metabolismo , Estudos Cross-Over , Esquema de Medicação , Feminino , Masculino , Propofol/sangue , Propofol/farmacocinética , Estudos ProspectivosRESUMO
OBJECTIVE: The purpose of this study was to prospectively evaluate the effect of benzyl alcohol, a common preservative in normal saline, on postprocedural pain after intraarticular injection for direct shoulder MR arthrography. SUBJECTS AND METHODS: From April 2011 through January 2013, 138 patients underwent direct shoulder MR arthrography. Using the Wong-Baker Faces Pain Scale, patients were asked to report their shoulder pain level immediately before and immediately after the procedure and then were contacted by telephone 6, 24, and 48 hours after the procedure. Fourteen patients did not receive the prescribed amount of contrast agent for diagnostic reasons or did not complete follow-up. Sixty-two patients received an intraarticular solution including preservative-free normal saline (control group) and 62 patients received an intraarticular solution including normal saline with 0.9% benzyl alcohol as a contrast diluent (test group). Patients were randomized as to which intraarticular diluent they received. Fluoroscopic and MR images were reviewed for extracapsular contrast agent administration or extravasation, full-thickness rotator cuff tears, and adhesive capsulitis. The effect of preservative versus control on pain level was estimated with multiple regression, which included time after procedure as the covariate and accounted for repeated measures over patients. RESULTS: Pain scale scores were significantly (p = 0.0382) higher (0.79 units; 95% CI, 0.034-1.154) with benzyl alcohol preservative compared with control (saline). In both study arms, the pain scale scores decreased slightly after the procedure, increased by roughly 1 unit over baseline for the test group and 0.3 unit over baseline for the control group by 6 hours after the procedure, were 0.50 unit over baseline for the test group and 0.12 unit over baseline for the control group at 24 hours, then fell to be slightly greater than baseline at 48 hours with benzyl alcohol and slightly less than baseline without benzyl alcohol. These trends over time were highly significant (p < 0.0001). CONCLUSION: Shoulder arthrography is often associated with postprocedural discomfort that begins immediately after the procedure and resolves by 48 hours. There is significantly increased patient discomfort at 6 and 48 hours when using normal saline preserved with benzyl alcohol as a diluent compared with using normal saline without preservative as a diluent.
Assuntos
Artrografia/efeitos adversos , Álcool Benzílico/efeitos adversos , Excipientes/efeitos adversos , Dor Pós-Operatória/induzido quimicamente , Cloreto de Sódio/efeitos adversos , Adolescente , Adulto , Álcool Benzílico/administração & dosagem , Meios de Contraste/administração & dosagem , Meios de Contraste/efeitos adversos , Meios de Contraste/química , Excipientes/química , Feminino , Humanos , Injeções Intra-Articulares/efeitos adversos , Masculino , Pessoa de Meia-Idade , Medição da Dor/efeitos dos fármacos , Dor Pós-Operatória/diagnóstico , Conservantes Farmacêuticos/efeitos adversos , Conservantes Farmacêuticos/química , Cloreto de Sódio/administração & dosagem , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: There are two components to the clinical efficacy of pediculicides: (i) efficacy against the crawling-stages (lousicidal efficacy); and (ii) efficacy against the eggs (ovicidal efficacy). Lousicidal efficacy and ovicidal efficacy are confounded in clinical trials. Here we report on a trial that was specially designed to rank the clinical ovicidal efficacy of pediculicides. Eggs were collected, pre-treatment and post-treatment, from subjects with different types of hair, different coloured hair and hair of different length. METHOD: Subjects with at least 20 live eggs of Pediculus capitis (head lice) were randomised to one of three treatment-groups: a melaleuca oil (commonly called tea tree oil) and lavender oil pediculicide (TTO/LO); a eucalyptus oil and lemon tea tree oil pediculicide (EO/LTTO); or a "suffocation" pediculicide. Pre-treatment: 10 to 22 live eggs were taken from the head by cutting the single hair with the live egg attached, before the treatment (total of 1,062 eggs). TREATMENT: The subjects then received a single treatment of one of the three pediculicides, according to the manufacturers' instructions. Post-treatment: 10 to 41 treated live eggs were taken from the head by cutting the single hair with the egg attached (total of 1,183 eggs). Eggs were incubated for 14 days. The proportion of eggs that had hatched after 14 days in the pre-treatment group was compared with the proportion of eggs that hatched in the post-treatment group. The primary outcome measure was % ovicidal efficacy for each of the three pediculicides. RESULTS: 722 subjects were examined for the presence of eggs of head lice. 92 of these subjects were recruited and randomly assigned to: the "suffocation" pediculicide (n = 31); the melaleuca oil and lavender oil pediculicide (n = 31); and the eucalyptus oil and lemon tea tree oil pediculicide (n = 30 subjects). The group treated with eucalyptus oil and lemon tea tree oil had an ovicidal efficacy of 3.3% (SD 16%) whereas the group treated with melaleuca oil and lavender oil had an ovicidal efficacy of 44.4% (SD 23%) and the group treated with the "suffocation" pediculicide had an ovicidal efficacy of 68.3% (SD 38%). CONCLUSION: Ovicidal efficacy varied substantially among treatments, from 3.3% to 68.3%. The "suffocation" pediculicide and the melaleuca oil and lavender oil pediculicide (TTO/LO) were significantly more ovicidal than eucalyptus oil and lemon tea tree oil pediculicide (EO/LTTO) (P < 0.0001). Ranking: 1. "Suffocation" pediculicide (68.3% efficacy against eggs); 2. Melaleuca oil and lavender oil (44.4%) pediculicide; 3. Eucalyptus oil and lemon tea tree oil (3.3%) pediculicide. The "suffocation" pediculicide and TTO/LO are also highly efficacious against the crawling-stages. Thus, the "suffocation" pediculicide and TTO/LO should be recommended as first line treatments.
Assuntos
Inseticidas/uso terapêutico , Leptospermum , Infestações por Piolhos/tratamento farmacológico , Melaleuca , Óleos Voláteis/uso terapêutico , Óvulo/efeitos dos fármacos , Pediculus/efeitos dos fármacos , Fitoterapia , Óleos de Plantas/uso terapêutico , Dermatoses do Couro Cabeludo/tratamento farmacológico , Óleo de Melaleuca/uso terapêutico , Acrilatos/administração & dosagem , Acrilatos/farmacologia , Acrilatos/uso terapêutico , Animais , Álcool Benzílico/administração & dosagem , Álcool Benzílico/farmacologia , Álcool Benzílico/uso terapêutico , Criança , Pré-Escolar , Método Duplo-Cego , Combinação de Medicamentos , Etilaminas/administração & dosagem , Etilaminas/farmacologia , Etilaminas/uso terapêutico , Eucalyptus , Óleo de Eucalipto , Hexoses/administração & dosagem , Hexoses/farmacologia , Hexoses/uso terapêutico , Humanos , Inseticidas/administração & dosagem , Inseticidas/farmacologia , Lavandula , Infestações por Piolhos/parasitologia , Óleo Mineral/administração & dosagem , Óleo Mineral/farmacologia , Óleo Mineral/uso terapêutico , Monoterpenos/administração & dosagem , Monoterpenos/farmacologia , Monoterpenos/uso terapêutico , Óleos Voláteis/administração & dosagem , Óleos Voláteis/farmacologia , Óvulo/crescimento & desenvolvimento , Pediculus/crescimento & desenvolvimento , Óleos de Plantas/administração & dosagem , Óleos de Plantas/farmacologia , Polissorbatos/administração & dosagem , Polissorbatos/farmacologia , Polissorbatos/uso terapêutico , Dermatoses do Couro Cabeludo/parasitologia , Óleo de Melaleuca/administração & dosagem , Óleo de Melaleuca/farmacologiaRESUMO
Benzyl alcohol lotion 5% (BAL 5%) is a non-neurotoxic topical head lice treatment that is safe and effective in children as young as 6 months of age. The safety and efficacy of this pediculicide has been studied in 695 (confirm number) subjects in all phases of clinical development. Scanning electron micrographs (SEM) demonstrated that the active agent appears to stun the breathing spiracles open, enabling the vehicle to penetrate the respiratory mechanism (spiracles), therefore asphyxiating the lice. Initial phase II trials compared this novel product to RID using identical volumes of treatment (4 oz/application) and yielding, almost, identical efficacy. This outcome pointed to the significant importance of completely saturating the hair with the product in order to achieve maximum treatment success. A second phase II trial, which allowed the use of sufficient product to saturate the hair, resulted in 100% efficacy after both 10 and 30 minute treatments. A third phase II trial verified an effective dose. Phase III trials compared BAL 5% to vehicle placebo for two 10-minute applications. It proved to be safe and effective (p < 0.001) for treatment of head lice and is the first FDA-approved non-neurotoxic lice treatment, now available in the United States as Ulesfia lotion.
Assuntos
Álcool Benzílico/administração & dosagem , Infestações por Piolhos/tratamento farmacológico , Pediculus/efeitos dos fármacos , Dermatoses do Couro Cabeludo/tratamento farmacológico , Administração Tópica , Animais , Álcool Benzílico/efeitos adversos , Criança , Pré-Escolar , Humanos , Lactente , Resultado do TratamentoRESUMO
Synthol consists usually of oil, benzyl alcohol and lidocain. It consists of 85% of oil (normally it is oil built by medium-length MTC chains because it gives the best effects), 7,5% of lidocain (painkiller), 7,5% of alcohol (to sterilize the mixture). Synthol is a substance used by body builders as a temporary implant which is injected deeply into the muscle. The enlargement effects are immediate. Synthol is used in small groups of muscles to enlarge their volume (for example triceps, biceps, deltoids, muscles of the calf). Some serious drawbacks can be visible while using synthol. The muscles deform and become unnaturally shaped. The side effects of synthol are manifold and they can also cause a damage of nerves, oil embolic of the pulmonary, occlusion of the pulmonary artery, myocardial infarction, cerebral stroke and infectious complications.
Assuntos
Álcool Benzílico/administração & dosagem , Dopagem Esportivo , Lidocaína/administração & dosagem , Músculo Esquelético/efeitos dos fármacos , Triglicerídeos/administração & dosagem , Levantamento de Peso , Álcool Benzílico/efeitos adversos , Humanos , Infecções/etiologia , Injeções Intramusculares , Lidocaína/efeitos adversos , Infarto do Miocárdio/etiologia , Embolia Pulmonar/etiologia , Somatotipos , Acidente Vascular Cerebral/etiologia , Triglicerídeos/efeitos adversosAssuntos
Anestésicos Locais/administração & dosagem , Álcool Benzílico/administração & dosagem , Injeções/efeitos adversos , Lidocaína/administração & dosagem , Dor/prevenção & controle , Combinação de Medicamentos , Ferimentos Oculares Penetrantes/etiologia , Ferimentos Oculares Penetrantes/prevenção & controle , Humanos , Injeções/métodos , Dor/etiologiaRESUMO
An accurate, sensitive and selective reversed-phase micellar liquid chromatographic method was developed for simultaneous determination of benzyl alcohol and benzaldehyde. This method was applied in different injectable formulations containing diclofenac, piroxicam, lincomycin and clindamycin. The method showed excellent linearity in the range of 10-100 microg mL(-1) and 1-20 microg mL(-1) with the limit of detection (S/N = 3) 0.25 microg mL(-1) (2.3 x 10(-6) mol L(-1)) and 0.12 microg mL(-1) (1.13 x 10(-6) mol L(-1)) for benzyl alcohol and benzaldehyde, respectively. The suggested method was successfully applied to the analysis of the studied drugs in bulk with average recoveries of 100.1 +/- 1.0% for benzyl alcohol and 100.4 +/- 1.6% for benzaldehyde, and to the determination of benzyl alcohol and benzaldehyde in injectable formulations with the respective average recoveries of 99.8 +/- 0.3 and 100.0 +/- 0.4%.
Assuntos
Anestésicos Locais/análise , Benzaldeídos/análise , Álcool Benzílico/análise , Cromatografia Capilar Eletrocinética Micelar/métodos , 1-Propanol/análise , 1-Propanol/química , Algoritmos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/química , Benzaldeídos/metabolismo , Benzaldeídos/normas , Álcool Benzílico/administração & dosagem , Álcool Benzílico/química , Calibragem , Cromatografia Capilar Eletrocinética Micelar/instrumentação , Cromatografia Capilar Eletrocinética Micelar/normas , Injeções , Modelos Lineares , Oxirredução , Conservantes Farmacêuticos/análise , Conservantes Farmacêuticos/química , Reprodutibilidade dos Testes , Dodecilsulfato de Sódio/análise , Dodecilsulfato de Sódio/químicaRESUMO
INTRODUCTION: The pharmacokinetics of excipients in neonates differs from that of older children. In a recent pan--European survey, two thirds of neonates received at least one potentially harmful excipient, such as ethanol and benzoates. The content of sweeteners varied by route of administration (more common by enteral than parenteral route), and regional differences were revealed. The survey did not identify if the content of excipients was more pronounced in medications prescribed for specific medical diseases, e.g. more common in cardiovascular conditions than lung diseases. Furthermore, the quantitative amount of e.g. ethanol in the multi-medicated neonate has not been investigated. The aim of the present study was to quantify the total amount of excipients administered to poly-medicated neonatal and paediatric patients during hospitalisation; and to investigate if any particular medical diseases are treated with potentially harmful excipients. METHODS: This is a retrospective cohort study based on chart-audit on multi-medicated patients ≤ 5 years of age treated at the Rigshospitalet, Denmark. Preparations with ethanol, propylene glycol, benzyl alcohol, parabens, acesulfame p, aspartame, glycerol, sorbitol and polysorbate-80 will be recorded and cumulative amounts will be calculated. CONCLUSION: By quantifying the amount of harmful excipients to which paediatric patients are exposed, the study will contribute to a risk/benefit assessment of the medication standards of neonatal and paediatric patients. FUNDING: The Danish Council for Independent Research, grant-id: DFF - 6110-00266. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov (reg. no. NCT02545712).
Assuntos
Excipientes/administração & dosagem , Auditoria Médica , Aspartame/administração & dosagem , Álcool Benzílico/administração & dosagem , Criança , Pré-Escolar , Etanol/administração & dosagem , Glicerol/administração & dosagem , Humanos , Lactente , Recém-Nascido , Propilenoglicol/administração & dosagem , Projetos de Pesquisa , Estudos Retrospectivos , Tiazinas/administração & dosagemRESUMO
Sustained release of lipophilic compounds can be achieved with oil depots. These parenteral formulations are generally injected in the vastus lateralis and deltoid muscle. It is known that the absorption rate differs between these two muscles. The reason for this is not fully understood. The aim of the current study was to investigate the fate of an oil depot in different tissues to elucidate whether the disappearance rate of oil is the cause of observed differences in absorption rate. A study with healthy volunteers was conducted to determine 1.0mL oil depots in the vastus lateralis and deltoid muscle for two weeks. The spatial distribution of the oil depots was determined using MRI. Additionally, a study in rats was conducted to microscopically examine the oil immediately and after 31days of injection. All rats were injected with a 0.1mL oil depot with and without benzyl alcohol (BOH), a commonly used excipient in oil depots. In humans, it was shown that all oil depots were equal in volume and surface area directly after injection. Moreover, the disappearance rate for all oil depots was similar; within one week there was no depot visible anymore by MRI. This in contrast to the depots in rats, which were still microscopically visible after 31days. It is concluded from these observations that the oil is dispersed to small droplets in the course of time. The resulting increase in surface area does not lead to an increase in absorption rate however. The results of this paper show that the variation in drug absorption as found for the two muscles is not caused by a distinction in surface areas or disappearance rates of the oil depots. Therefore, it is argued that the local tissue drainage (e.g. lymph flow) plays a considerable role in drug absorption from oil depots, whereby the lymph flow differs between the muscles.
Assuntos
Absorção Intramuscular , Músculo Esquelético/metabolismo , Óleo de Gergelim/administração & dosagem , Óleo de Gergelim/farmacocinética , Adulto , Animais , Álcool Benzílico/administração & dosagem , Preparações de Ação Retardada , Humanos , Injeções Intramusculares , Imageamento por Ressonância Magnética , Masculino , Ratos , Ratos WistarRESUMO
The head louse (Pediculus humanus capitis) is a blood-sucking arthropod of the suborder Anoplura. Infestation continues in epidemic proportions in children of all socioeconomic groups. Although not implicated as a disease vector, infestation can lead to considerable distress, missed days of school, and secondary infections. Pyrethroids are recommended for treatment, but resistance is common. Newer agents, including benzyl alcohol and spinosad, have been developed to address this gap in care.
Assuntos
Inseticidas/administração & dosagem , Infestações por Piolhos/epidemiologia , Pediculus/efeitos dos fármacos , Animais , Álcool Benzílico/administração & dosagem , Criança , Combinação de Medicamentos , Desenho de Fármacos , Humanos , Resistência a Inseticidas , Infestações por Piolhos/tratamento farmacológico , Macrolídeos/administração & dosagem , Piretrinas/administração & dosagemRESUMO
PURPOSE: This study aimed to review the incidence and clinical outcome of presumed sterile endophthalmitis after the off-label use of intravitreal Kenalog injections (triamcinolone acetonide with 1.5% benzyl alcohol) and to compare it with the presumed sterile endophthalmitis incidence after intravitreal Kenacort-A (0.99% benzyl alcohol) at our center. DESIGN: This was a single-center, retrospective, consecutive, interventional case series of all patients who underwent intravitreal Kenalog injections at Hong Kong Eye Hospital from November 1, 2009, to July 31, 2012. METHODS: This was a retrospective medical records review. RESULTS: A total of 81 intravitreal Kenalog injections were performed. Ten eyes (12.3%) developed presumed sterile endophthalmitis, presenting clinically with dense anterior chamber cells, fibrin, hypopyon, and vitritis. All cases were treated with topical steroids and antibiotics. Although the inflammation resolved eventually in all cases, 2 eyes developed complications, resulting in eventual loss of best corrected visual acuity: one developed rhegmatogenous retinal detachment with choroidal detachment, and another developed vitreous hemorrhage. CONCLUSIONS: The rate of presumed sterile endophthalmitis after Kenalog injection is much higher than our previous experience with Kenacort-A. To the best of our knowledge, this is the first study reporting the incidence of presumed sterile endophthalmitis using intravitreal Kenalog and Kenacort in the same center using the same injection technique. We believe that it may be due to a difference in the concentration of the preservative. Although sterile endophthalmitis is generally thought to run a benign course, this study has shown that serious complications may occur.
Assuntos
Endoftalmite/induzido quimicamente , Endoftalmite/epidemiologia , Glucocorticoides/efeitos adversos , Injeções Intravítreas/efeitos adversos , Triancinolona Acetonida/efeitos adversos , Álcool Benzílico/administração & dosagem , Doenças da Coroide/etiologia , Endoftalmite/complicações , Glucocorticoides/administração & dosagem , Hong Kong/epidemiologia , Humanos , Incidência , Conservantes Farmacêuticos , Descolamento Retiniano/etiologia , Estudos Retrospectivos , Triancinolona Acetonida/administração & dosagem , Acuidade Visual , Hemorragia Vítrea/etiologiaRESUMO
The penetration of benzyl alcohol (BA) through split-thickness cadaver skin was measured in nonoccluded Franz cells placed in a fume hood. BA, dissolved in a small volume of ethanol and spiked with (14)C radiolabel, was applied to skin at nine doses ranging from 0.9 to 10600 microg/cm(2). The percentage of radioactivity penetrated after 24 h increased gradually with dose, ranging from 19.8 +/- 2.9% at the lowest dose to 29.2 +/- 3.0% at the highest. Less than 4% of the radioactivity was retained in the tissue at 24 h; the remainder was considered to be evaporated. These data and those from a previous study were analyzed in terms of a finite dose diffusion/evaporation model. The analysis showed that the increase in BA absorption with dose was consistent with a threefold increase in BA diffusivity in the stratum corneum, as its concentration increased from tracer levels to saturation. The variable diffusivity model was able to describe the combined observations from the two studies to within an rms error of 4.2% of dose. A method of estimating the diffusion model parameters independently of the experiment was found to yield good agreement with the experimentally-derived values at low and moderate doses.
Assuntos
Álcool Benzílico/farmacocinética , Pele/metabolismo , Administração Cutânea , Álcool Benzílico/administração & dosagem , Radioisótopos de Carbono/metabolismo , Difusão , Humanos , Modelos Estatísticos , Absorção Cutânea/efeitos dos fármacos , Fatores de Tempo , VolatilizaçãoRESUMO
OBJECTIVE: To evaluate the in vitro activity of an ear rinse (ER) containing tromethamine, EDTA, and benzyl alcohol on bacterial pathogens from dogs with otitis. SAMPLE POPULATION: Organisms were collected from ear swab specimens from the external and middle ear and included Staphylococcus spp (n = 11; Staphylococcus intermedius [7] and Staphylococcus spp [4]), Pseudomonas aeruginosa (5), Proteus spp (5), beta-hemolytic streptococcus (11), and 1 control strain of each organism. PROCEDURES: 3 test solutions were evaluated including EDTA, tromethamine, and benzyl alcohol (ER); EDTA and tromethamine (ER without benzyl alcohol [ER - BA]); and purified water. Ten-milliliter aliquots of each test solution were transferred into 36 tubes and inoculated with one of the organisms. Samples were retrieved from each tube at 0, 15, 30, 45, and 60 minutes, transferred to Petri dishes, mixed with soybean-casein digest agar, and incubated. After incubation, plates were examined for growth, and the number of colonies was expressed as CFU per milliliter. RESULTS: ER significantly decreased bacterial growth in vitro of P aeruginosa and beta-hemolytic streptococcal organisms within 15 minutes, Proteus spp within 30 minutes, and Staphylococcus spp within 60 minutes. Comparatively, the presence of benzyl alcohol in ER significantly decreased bacterial growth of beta-hemolytic streptococcus and Proteus spp. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of results of this study, future studies should be performed to evaluate the in vivo efficacy of ER alone as a treatment for otic infections caused by beta-hemolytic streptococcus, P aeruginosa, and Proteus spp and of ER combined with an antimicrobial agent for otic infections caused by Staphylococcus spp.
Assuntos
Bactérias/efeitos dos fármacos , Álcool Benzílico/farmacologia , Doenças do Cão/microbiologia , Ácido Edético/farmacologia , Otite Externa/veterinária , Otite Média/veterinária , Trometamina/farmacologia , Animais , Álcool Benzílico/administração & dosagem , Cães , Formas de Dosagem , Ácido Edético/administração & dosagem , Otite Externa/microbiologia , Otite Média/microbiologia , Trometamina/administração & dosagemRESUMO
Pharmaceutical oil depots are meant to release active substances at a sustained rate. Most of these depots contain benzyl alcohol (BOH) to facilitate the production and administration. Because BOH changes the solubility of components in both the body fluid and the oil formulation, it is relevant to know the change in the BOH concentration in the oil over time. In this study, volunteers were subcutaneously injected with an oil depot that contained 10% BOH, nandrolone decanoate, and cholecalciferol. The aim of this study was to determine the pharmacokinetic profiles of BOH and its metabolites benzoic acid and hippuric acid simultaneously in serum to estimate the BOH release out of the depot. For this, an HPLC bioassay was developed and adequately validated. Hereafter, the bioassay was applied to serum samples obtained at several time points between 0 and 35 days. BOH appeared immediately in serum after injection. The pharmacokinetic profile revealed that all BOH was depleted from the depot within 52 h after injection. Thus, the partition coefficient of active substances between the oil formulation and the body tissue changes rapidly in the first days after injection but will remain constant hereafter.
Assuntos
Álcool Benzílico/administração & dosagem , Álcool Benzílico/sangue , Preparações de Ação Retardada/química , Óleos/química , Idoso , Ácido Benzoico/sangue , Ácido Benzoico/metabolismo , Álcool Benzílico/metabolismo , Cromatografia Líquida de Alta Pressão , Feminino , Hipuratos/sangue , Hipuratos/metabolismo , HumanosRESUMO
Oil depots are parenteral drug formulations meant for sustained release of lipophilic compounds. Until now, a comprehensive understanding of the mechanism of drug absorption from oil depots is lacking. The aim of this paper was to fill this gap. A clinical study with healthy volunteers was conducted. An oil depot with nandrolone decanoate and benzyl alcohol was subcutaneously administered in the upper arm of female volunteers. Pharmacokinetic profiles of both substances were related to each other and to literature data. Benzyl alcohol absorbs much more rapidly than nandrolone. In detail, it appears that benzyl alcohol enters the central compartment directly, while nandrolone decanoate is recovered in serum after a lag time. This lag time is also seen in literature data, although not reported explicitly. The absorption of nandrolone is enhanced by the presence of benzyl alcohol. This is most likely an effect of altered oil viscosity and partition coefficient between the oil and aqueous phase. The absorption rate constant of compounds is found to be related to the logP of the solubilized prodrug. The absorption rate is however not only determined by the physico-chemical properties of the formulation but also by the tissue properties. Here, it is argued that lymphatic flow must be considered as a relevant parameter.
Assuntos
Álcool Benzílico/administração & dosagem , Álcool Benzílico/farmacocinética , Nandrolona/análogos & derivados , Óleo de Gergelim/administração & dosagem , Óleo de Gergelim/farmacocinética , Absorção Fisiológica , Idoso , Idoso de 80 Anos ou mais , Androgênios/administração & dosagem , Androgênios/sangue , Androgênios/química , Androgênios/farmacocinética , Álcool Benzílico/sangue , Álcool Benzílico/química , Formas de Dosagem , Feminino , Humanos , Injeções Intramusculares , Injeções Subcutâneas , Nandrolona/administração & dosagem , Nandrolona/sangue , Nandrolona/química , Nandrolona/farmacocinética , Decanoato de Nandrolona , Óleo de Gergelim/química , ViscosidadeRESUMO
Acetaminophen (APAP) hepatotoxicity is a serious public health problem in western countries. Current treatment options for APAP poisoning are limited and novel therapeutic intervention strategies are needed. A recent publication suggested that benzyl alcohol (BA) protects against APAP hepatotoxicity and could serve as a promising antidote for APAP poisoning. To assess the protective mechanisms of BA, C56Bl/6J mice were treated with 400 mg/kg APAP and/or 270 mg/kg BA. APAP alone caused extensive liver injury at 6 h and 24 h post-APAP. This injury was attenuated by BA co-treatment. Assessment of protein adduct formation demonstrated that BA inhibits APAP metabolic activation. In support of this, in vitro experiments also showed that BA dose-dependently inhibits cytochrome P450 activities. Correlating with the hepatoprotection of BA, APAP-induced oxidant stress and mitochondrial dysfunction were reduced. Similar results were obtained in primary mouse hepatocytes. Interestingly, BA alone caused mitochondrial membrane potential loss and cell toxicity at high doses, and its protective effect could not be reproduced in primary human hepatocytes (PHH). We conclude that BA protects against APAP hepatotoxicity mainly by inhibiting cytochrome P450 enzymes in mice. Considering its toxic effect and the loss of protection in PHH, BA is not a clinically useful treatment option for APAP overdose patient.
Assuntos
Acetaminofen/toxicidade , Álcool Benzílico/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Sistema Enzimático do Citocromo P-450/metabolismo , Hepatócitos/efeitos dos fármacos , Mitocôndrias Hepáticas/efeitos dos fármacos , Analgésicos não Narcóticos/toxicidade , Anestésicos Locais/toxicidade , Animais , Álcool Benzílico/administração & dosagem , Álcool Benzílico/efeitos adversos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
A 53-year-old African-American man with relapsed non-Hodgkin's lymphoma developed seizures and respiratory arrest 2 hours after an infusion of high-dose etoposide in preparation for an autologous bone marrow transplant. Laboratory tests revealed both rapid hemolysis and severe metabolic acidosis. The patient died the following day. Based on toxicities observed, we suspect that our patient possessed an ethnic polymorphism of the enzyme alcohol dehydrogenase. Further research is required to determine the relationship between the benzyl alcohol metabolic rate and toxicity and genetic polymorphisms of alcohol dehydrogenase in African-Americans.
Assuntos
Acidose/induzido quimicamente , Álcool Benzílico/efeitos adversos , Etoposídeo/efeitos adversos , Hemólise , Linfoma não Hodgkin/tratamento farmacológico , Insuficiência Respiratória/induzido quimicamente , Convulsões/induzido quimicamente , África/etnologia , Álcool Desidrogenase/genética , Álcool Benzílico/administração & dosagem , Combinação de Medicamentos , Evolução Fatal , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genéticaRESUMO
Adverse reactions to medication are well recognised although information on the incidence in children is lacking. Adverse reactions have also been attributed to a range of pharmaceutical excipients. This is a report of an adverse reaction to the excipient in clindamycin injection.