RESUMEN
Transient permeability enhancers (PEs), such as caprylate, caprate, and salcaprozate sodium (SNAC), improve the bioavailability of poorly permeable macromolecular drugs. However, the effects are variable across individuals and classes of macromolecular drugs and biologics. Here, we examined the influence of bile compositions on the ability of membrane incorporation of three transient PEs-caprylate, caprate, and SNAC-using coarse-grained molecular dynamics (CG-MD). The availability of free PE monomers, which are important near the absorption site, to become incorporated into the membrane was higher in fasted-state fluids than that in fed-state fluids. The simulations also showed that transmembrane perturbation, i.e., insertion of PEs into the membrane, is a key mechanism by which caprylate and caprate increase permeability. In contrast, SNAC was mainly adsorbed onto the membrane surface, indicating a different mode of action. Membrane incorporation of caprylate and caprate was also influenced by bile composition, with more incorporation into fasted- than fed-state fluids. The simulations of transient PE interaction with membranes were further evaluated using two experimental techniques: the quartz crystal microbalance with dissipation technique and total internal reflection fluorescence microscopy. The experimental results were in good agreement with the computational simulations. Finally, the kinetics of membrane insertion was studied with CG-MD. Variation in micelle composition affected the insertion rates of caprate monomer insertion and expulsion from the micelle surface. In conclusion, this study suggests that the bile composition and the luminal composition of the intestinal fluid are important factors contributing to the interindividual variability in the absorption of macromolecular drugs administered with transient PEs.
Asunto(s)
Bilis/química , Caprilatos/administración & dosificación , Caprilatos/metabolismo , Permeabilidad de la Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Decanoatos/administración & dosificación , Decanoatos/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Sustancias Macromoleculares/administración & dosificación , Ácidos y Sales Biliares/metabolismo , Disponibilidad Biológica , Voluntarios Sanos , Humanos , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Simulación de Dinámica Molecular , Fosfolípidos/metabolismoRESUMEN
BACKGROUND: Synthetic vascular material use, particularly polytetrafluoroethylene- (PTFE) -based, can be associated with bleeding, which may increase operative time and blood loss. None of the commercially available sealants designed to ensure hemostasis combine bioresorption, high viscosity, hydrophobicity, and compliance with the underlying tissue and on-demand activation. METHODS: A study was designed to assess the biocompatibility and in-vivo performance and bioresorption of a new synthetic on-demand light-activated poly(glycerol-sebacate) acrylate- (PGSA) -based SETALIUM™ Vascular Sealant (TISSIUM, Paris, France) in three large animal studies of open vascular carotid and aortic surgery. The pre-clinical results were then translated into a clinical setting in a prospective, single-arm multicenter study in patients requiring carotid endarterectomy using an ePTFE patch. RESULTS: The biocompatibility testing showed that the PGSA-based SETALIUM™ Vascular Sealant did not induce any significant toxic reaction at a standard clinical dose nor at doses up to 40 times the equivalent intended clinical dose. The PGSA-based sealant was shown to be non-pyrogenic, non-sensitizing, non-irritant, non-clastogenic, and non-mutagenic. The animal studies showed excellent performance and safety results, with clinically significant hemostasis achieved in 100% of the animals in both carotid and aorta studies and excellent local tolerance. Histopathology and morphometric analyses showed surface-based gradual and sustained bioresorption of the PGSA-based sealant up to 86% at 12 months. In the clinical study, the application of the PGSA-based sealant resulted in good performance and safety, with immediate hemostasis achieved in 84% of the cases and no adverse event related to the sealant reported through the one-year follow-up. CONCLUSIONS: The new synthetic on-demand light activated PGSA-based SETALIUM™ Vascular Sealant investigated in our studies demonstrated good biocompatibility, sustained and gradual surface based bioresorption, and acceptable safety profile in animal studies. In addition, the first in-human use showed that the sealant is a safe and effective alternative to achieve fast and controlled hemostasis in vascular carotid reconstructions. A larger randomized controlled study will allow further validation of these encouraging preliminary results.
Asunto(s)
Acrilatos/administración & dosificación , Angioplastia/efectos adversos , Aorta Torácica/cirugía , Arterias Carótidas/cirugía , Decanoatos/administración & dosificación , Endarterectomía Carotidea/efectos adversos , Glicerol/análogos & derivados , Hemorragia/prevención & control , Técnicas Hemostáticas , Polímeros/administración & dosificación , Adhesivos Tisulares/administración & dosificación , Acrilatos/efectos adversos , Anciano , Anciano de 80 o más Años , Angioplastia/instrumentación , Animales , Decanoatos/efectos adversos , Endarterectomía Carotidea/instrumentación , Femenino , Glicerol/administración & dosificación , Glicerol/efectos adversos , Técnicas Hemostáticas/efectos adversos , Humanos , Masculino , Ensayo de Materiales , Persona de Mediana Edad , Modelos Animales , Polímeros/efectos adversos , Estudios Prospectivos , Oveja Doméstica , Factores de Tiempo , Adhesivos Tisulares/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: To compare in a generalizable sample/setting objective outcomes in patients receiving first-generation antipsychotic long-acting injectables (FGA-LAIs) or risperidone-LAI (RIS-LAI). METHODS: Nationwide, retrospective inception cohort study of adults with International Classification of Diseases-10 schizophrenia using Danish registers from 1995 to 2009 comparing outcomes between clinician's/patient's choice treatment with FGA-LAIs or RIS-LAI. Primary outcome was time to psychiatric hospitalization using Cox-regression adjusting for relevant covariates. Secondary outcomes included time to all-cause discontinuation and psychiatric hospitalization in patients without LAI possession gap >28 days, and number of bed-days after psychiatric hospitalization. RESULTS: Among 4532 patients followed for 2700 patient-years, 2078 received RIS-LAI and 2454 received FGA-LAIs (zuclopenthixol decanoate = 52.2%, perphenazine decanoate = 37.2%, haloperidol decanoate = 5.0%, flupenthixol decanoate = 4.4%, fluphenazine decanoate = 1.3%). RIS-LAI was similar to FGA-LAIs regarding time to hospitalization (RIS-LAI = 246.2±323.7 days vs FGA-LAIs = 276.6±383.3 days; HR = 0.95, 95% confidence interval (CI) = 0.87-1.03, P = 0.199) and time to all-cause discontinuation (RIS-LAI = 245.8±324.0 days vs FGA-LAIs = 287.0±390.9 days; HR = 0.93, 95% CI = 0.86-1.02, P = 0.116). Similarly, in patients without LAI discontinuation, RIS-LAI and FGA-LAIs did not differ regarding time to hospitalization (RIS-LAI = 175.0±268.1 days vs FGA-LAIs = 210.7±325.3 days; HR = 0.95, 95% CI = 0.86-1.04, P = 0.254). Finally, duration of hospitalization was also similar (incidence rate ratio = 0.97, 95% CI = 0.78-1.19, P = 0.744). Results were unchanged when analyzing only patients treated after introduction of RIS-LAI. CONCLUSIONS: In this nationwide cohort study, RIS-LAI was not superior to FGA-LAIs regarding time to psychiatric hospitalization, all-cause discontinuation, and duration of hospitalization. Given the cost of hospitalization and second-generation antipsychotic (SGA)-LAIs, these findings require consideration when making treatment choices, but also need to be balanced with the individual relevance of adverse effects/patient centered outcomes. In future, head-to-head trials and additional nationwide database studies including other SGA-LAIs is needed.
Asunto(s)
Antipsicóticos/farmacología , Decanoatos/farmacología , Evaluación de Resultado en la Atención de Salud , Sistema de Registros , Risperidona/farmacología , Esquizofrenia/tratamiento farmacológico , Adulto , Antipsicóticos/administración & dosificación , Decanoatos/administración & dosificación , Preparaciones de Acción Retardada , Dinamarca , Femenino , Estudios de Seguimiento , Hospitalización/estadística & datos numéricos , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Risperidona/administración & dosificación , Factores de TiempoRESUMEN
O objetivo deste estudo foi avaliar os efeitos e os métodos de aplicação dos aditivos foliares decanoato de nandrolona (esteroide anabolizante) a 0,5%, ácido ascórbico (vitamina C) a 0,5%, palmitato de retinol (vitamina A) a 0,5% e acetato de retinol (vitamina A) a 1,0% em alguns parâmetros biológicos do bicho-da-seda. No experimento do modo de aplicação (pulverização foliar antes do fornecimento, depois do fornecimento e por imersão antes do fornecimento) foram utilizados: decanoato de nandrolona 0,5%; ácido ascórbico 0,5%; e palmitato de retinol 0,5%. No ensaio de desenvolvimento do inseto foram avaliados: duração e viabilidade larval; peso de casulo; taxa de encasulamento; teor líquido de seda; longevidade de adultos; número de ovos por fêmea; e duração do período de subida ao bosque. Para o modo de aplicação determinaram-se: ganho de peso, comprimento, diâmetro do tórax e diâmetro do abdome de lagartas de 5º ínstar, assim como comprimento, diâmetro e peso de glândula sericígena. Os resultados mostraram que, apesar de o ácido ascórbico proporcionar os melhores valores para o desenvolvimento corpóreo das lagartas, este não corresponde a incrementos significativos na produção; o palmitato de retinol não melhora o desenvolvimento das lagartas; o acetato de retinol e o palmitato de retinol prolongam o período larval, sem, no entanto, alterar significativamente os parâmetros de produção; a imersão de folhas antes do fornecimento às lagartas é mais viável para a aplicação dos aditivos.(AU)
The present study was aimed to evaluate the effects of different methods of foliar application of the additives nandrolone decanoate (anabolic steroid) 0,5%; ascorbic acid (vitamin C) 0,5%; retinol palmitate (vitamin A) 0,5%; and retinol acetate (vitamin A) 1,0% on some biological parameters of the silkworm. The experiment of application method (foliar spray prior to delivery, after delivery and soaking before feeding) used: nandrolone decanoate 0.5%, ascorbic acid 0.5%, and retinol palmitate 0.5%. The test of insect development evaluated: duration and larval viability, weight of cocoon, cocooning rate, liquid silk content, adult longevity, number of eggs per female and rising up time. For the application of foliar additives, the following were determined: weight gain, length, diameter and abdomen diameter of fifth instar larvae, and length, diameter and weight of silk gland. The results showed that although ascorbic acid provided the best value for the development of the caterpillars body, it did not correspond to significant increase in production; retinol palmitate did not affect the larvae body development; retinol acetate and retinol palmitate prolong the larval period, without, however, significantly altering the production parameters. The immersion method of leaves before being delivered to the caterpillars is the most feasible for the foliar application of additives.(AU)
Asunto(s)
Bombyx/crecimiento & desarrollo , Decanoatos/administración & dosificación , Anabolizantes/administración & dosificación , Larva/crecimiento & desarrollo , InsectosRESUMEN
BACKGROUND: The objectives of this study were to evaluate the efficacy of poly(glycerol) sebacate (PGS) films for the prevention of visceroparietal peritoneal (VP) adhesions and demonstrate the ease of laparoscopic PGS film placement. Peritoneal adhesions occur in nearly 95% of all abdominal operations. VP adhesions can cause serious postoperative complications. The interposition of a barrier between damaged peritoneal areas during re-epithelialization has been shown to prevent adhesion formation. Current barrier products have serious drawbacks, including poor degradability, variable efficacy, and difficult handling characteristics. METHODS: The efficacy of PGS films to prevent VP adhesions was evaluated in a rat peritoneal adhesion model. The animals were evaluated for the presence of VP adhesions at 3, 5, and 8 weeks. The laparoscopic applicability of PGS films was demonstrated by placement into a juvenile porcine abdomen using standard laparoscopic equipment and techniques. RESULTS: A statistically significant 94% reduction in VP adhesion formation rate was observed between control animals (75%) and animals with a PGS film barrier (4.8%). PGS films were easily placed in the juvenile porcine abdomen and could be readily repositioned without material loss or tissue damage. CONCLUSION: PGS films possess a unique combination of properties, including biocompatibility, resorbability, and ease of handling. PGS barrier films were shown to be efficacious in reducing VP adhesions in the rat model. They also can be placed using standard laparoscopic techniques. These promising results suggest that PGS films will be effective barriers to adhesion formation for patients undergoing open and laparoscopic abdominal operations.
Asunto(s)
Materiales Biocompatibles , Decanoatos , Glicerol/análogos & derivados , Laparoscopía/métodos , Polímeros , Adherencias Tisulares/prevención & control , Animales , Materiales Biocompatibles/administración & dosificación , Decanoatos/administración & dosificación , Glicerol/administración & dosificación , Humanos , Obstrucción Intestinal/prevención & control , Masculino , Ensayo de Materiales , Modelos Animales , Enfermedades Peritoneales/patología , Enfermedades Peritoneales/prevención & control , Polímeros/administración & dosificación , Ratas , Ratas Wistar , Sus scrofa , Adherencias Tisulares/patologíaRESUMEN
No disponible
Asunto(s)
Masculino , Adulto , Humanos , Decanoatos/administración & dosificación , Flufenazina/administración & dosificación , Antipsicóticos/administración & dosificación , Errores de Medicación , Sobredosis de DrogaRESUMEN
Relata-se o tratamento de um caso de dermatite psicogênica em um cão Rottweiler macho, com idade de 13 meses, pesando 42 kg. O paciente apresentava graves lesões dermatológicas devidas a auto-mutilação por lambedura, em ambas as regiões metatarsianas, e a anamnese indicava que o distúrbio psíquico tivesse origem no estresse provocado por uma mudança ambiental. Prescreveu-se tratamento com um neuroléptico de ação prolongada, o decanoato de haloperidol, com dose calculada por meio de extrapolação alométrica interespecífica, usando-se como modelo a dose total humana de 100 mg/70 kg. A dose total calculada para o cão de 42 kg foi de 70 mg, sendo administrada semanalmente, durante seis semanas. Já na segunda semana a recuperação era satisfatória, sendo que a cura completa foi obtida no 28º dia de tratamento. Mantido em observação por um período de seis meses, o paciente não apresentou quaisquer sinais de recidiva. Os resultados indicam que a droga apresenta excelentes perspectivas para o tratamento desta dermatopatia canina, e que o método de extrapolação alométrica interespecífica é plenamente eficiente no estabelecimento de protocolos posológicos individualizados.
ABSTRACT: This paper reports the results of the treatment of a 13 month-old male Rottweiler dog, weighing 42 kg, affected by psychogenic dermatitis. The patient presented serious cutaneous lesions due to self-licking, affecting both metatarsal areas. Anamnesis indicated that the psychic disturbance was caused by stress provoked by an environmental change. It was prescribed haloperidol decanoate, a long-acting neuroleptic, with dose calculated by interspecifi c allometric scaling, using as model the human total dose of 100 mg/70 kg. The total dose calculated for the 42 kg dog was 70 mg, and it was administered weekly for six weeks. Clinical recovery was already satisfactory in the second week, and complete cure was obtained in the 28th day of treatment. The patient was monitored by a six months period and did not present any relapsing signs. The results indicate that the drug presents excellent perspectives for the treatment of this canine skin disease, and that the method of interespecifi c allometric scaling is effi cient in the establishment of individualized therapeutic protocols.KEY WORDS: psychogenic dermatitis, neuroleptic, haloperidol decanoate, allometric scaling, dog
RESUMEN: Relata-se el tratamiento de un caso de dermatitis psicogénica en un perro Rottweiler macho, con edad de 13 meses y peso de 42 kg. El paciente presentaba graves lesiones dermatológicas debidas a auto-mutilación por lamedura, en ambas las regiones metatarsianas, y la anamnesia indicaba que la enfermedad tuviese origen en el estrés provocado por un cambio ambiental. Se prescribió tratamiento con un agente neuroléptico de acción prolongada, el decanoato de haloperidol, con dosis calculada por extrapolación alométrica interespecífi ca, se usando como modelo la dosis total humana de 100 mg/70 kg. La dosis total calculada para el perro de 42 kg fue de 70 mg, sendo administrada semanalmente, durante seis semanas. La recuperación clínica ya era satisfactoria en la segunda semana, y la cura completa se obtuvo en el vigésimo octavo día de tratamiento. El paciente fue supervisado por un periodo de seis meses y no presentó ninguna señal de retorno de la enfermedad. Los resultados indican que la droga presenta perspectivas excelentes para el tratamiento de esta enfermedad en perros, y que el método de extrapolación alométrica descascarar es en el establecimiento de protocolos terapéuticos individualizados.
Asunto(s)
Enfermedades de la Piel , Antipsicóticos/administración & dosificación , Perros , Decanoatos/administración & dosificación , Dermatitis/prevención & control , Dermatitis/veterinariaRESUMEN
Biodegradable polymers have significant potential in biotechnology and bioengineering. However, for some applications, they are limited by their inferior mechanical properties and unsatisfactory compatibility with cells and tissues. A strong, biodegradable, and biocompatible elastomer could be useful for fields such as tissue engineering, drug delivery, and in vivo sensing. We designed, synthesized, and characterized a tough biodegradable elastomer from biocompatible monomers. This elastomer forms a covalently crosslinked, three-dimensional network of random coils with hydroxyl groups attached to its backbone. Both crosslinking and the hydrogen-bonding interactions between the hydroxyl groups likely contribute to the unique properties of the elastomer. In vitro and in vivo studies show that the polymer has good biocompatibility. Polymer implants under animal skin are absorbed completely within 60 days with restoration of the implantation sites to their normal architecture.
Asunto(s)
Implantes Absorbibles , Materiales Biocompatibles/síntesis química , Decanoatos/síntesis química , Ácidos Decanoicos/química , Ácidos Dicarboxílicos , Glicerol/química , Glicerol/síntesis química , Ensayo de Materiales , Modelos Moleculares , Polímeros/síntesis química , Células 3T3/metabolismo , Animales , Decanoatos/administración & dosificación , Elasticidad , Elastómeros/síntesis química , Elastómeros/toxicidad , Femenino , Glicerol/administración & dosificación , Glicerol/análogos & derivados , Ácido Láctico/administración & dosificación , Ácido Láctico/química , Ensayo de Materiales/métodos , Ratones , Ácido Poliglicólico/administración & dosificación , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros/administración & dosificación , Polímeros/química , Ratas , Piel/metabolismo , Estrés Mecánico , Resistencia a la TracciónRESUMEN
PURPOSE: Sodium N-[10-(2-hydroxybenzoyl)amino]decanoate (SNAD) is a novel carrier that allows the gastrointestinal absorption of low-molecular weight heparin (LMWH). The purpose of this experiment was to evaluate oral LMWH with SNAD for the prevention of deep venous thrombosis. METHODS: Sixty Sprague-Dawley rats were equally assigned to five experimental groups: group 1 (control), oral saline solution; group 2, oral LMWH (15 mg/kg); group 3, oral SNAD (300 mg/kg); group 4, subcutaneous LMWH (5 mg/kg); and group 5, oral LMWH (15 mg/kg) and SNAD (300 mg/kg). After treatment, the jugular vein was isolated, occluded, and bathed in an ethanol and formalin solution for 2 minutes. Two hours later, the vessel was examined for patency, presence of thrombus, and thrombus weight. Serum measurement of anti-factor Xa activity was performed in a separate set of 30 rats, which were placed into the following four groups: group A, LMWH (5 mg/kg); group B, oral LMWH (15 mg/kg) and SNAD (300 mg/kg); group C, oral LMWH (15 mg/kg); and group D, SNAD (300 mg/kg). RESULTS: The animals that underwent oral LMWH/SNAD therapy had a statistically significant decrease in visible thrombi. The thrombus weight of the oral LMWH/SNAD group was significantly less than the weights of all other groups, except the subcutaneous LMWH group. Anti-factor Xa levels were significantly elevated in the LMWH/SNAD group. There was no statistically significant difference between the data for the oral LMWH/SNAD group and the subcutaneous LMWH group. CONCLUSION: The combination of oral LMWH and SNAD prevented deep venous thrombosis. The oral LMWH and SNAD therapy effected an increase in levels of anti-factor Xa.
Asunto(s)
Anticoagulantes/administración & dosificación , Decanoatos/administración & dosificación , Sistemas de Liberación de Medicamentos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Hidroxibenzoatos/administración & dosificación , Venas Yugulares , Trombosis de la Vena/prevención & control , Administración Oral , Animales , Distribución de Chi-Cuadrado , Portadores de Fármacos , Factor Xa/análisis , Inyecciones Subcutáneas , Absorción Intestinal , Placebos , Ratas , Ratas Sprague-Dawley , Grado de Desobstrucción Vascular , Trombosis de la Vena/patologíaRESUMEN
Because of the relatively poor intestinal absorption of ampicillin sodium, efforts have been made to enhance ampicillin absorption by co-administration of absorption promoters. In the present study the enhancing effect of sodium decanoate on rate and extent of rectal ampicillin absorption in rats has been evaluated after rate-controlled and site-controlled delivery of aqueous solutions. Rectal absorption without enhancer was extremely low (8 +/- 7%), and the addition of 0.032 M sodium decanoate gave comparable values. However, administration in 0.16 M decanoate considerably increased ampicillin bioavailability, to 79 +/- 30%, whereas the absorption rate was not significantly affected.
Asunto(s)
Ampicilina/administración & dosificación , Decanoatos/administración & dosificación , Ácidos Decanoicos/administración & dosificación , Absorción Intestinal/efectos de los fármacos , Administración Rectal , Ampicilina/farmacocinética , Animales , Preparaciones de Acción Retardada , Quimioterapia Combinada , Infusiones Intravenosas , Masculino , Ratas , Ratas EndogámicasRESUMEN
The treatment of alcoholism still presents great problems because a number of factors have to be taken into consideration. Tranquilizers and chlormethiazol are only justified in the detoxication phase. For the subsequent after-care, depot neuroleptics are recommended because of the uniformly high plasma level. We gave clopentixol decanoate - 100 mg i.m. - in two-weekly intervals. The symptoms caused by ethylism were adequately overcome without side effects. Clopentixol decanoate creates the basis for successful psychotherapy: only when the mood situation is compensated and the internal unrest overcome can verbal therapy be successful.
Asunto(s)
Alcoholismo/tratamiento farmacológico , Clopentixol/administración & dosificación , Decanoatos/uso terapéutico , Ácidos Decanoicos/uso terapéutico , Tioxantenos/administración & dosificación , Adulto , Clopentixol/análogos & derivados , Decanoatos/administración & dosificación , Preparaciones de Acción Retardada , Femenino , Humanos , Masculino , Persona de Mediana EdadAsunto(s)
Discinesia Biliar/diagnóstico por imagen , Enfermedades de la Vesícula Biliar/diagnóstico por imagen , Enfermedad de Hodgkin/complicaciones , Nandrolona/análogos & derivados , Adolescente , Niño , Preescolar , Colecistografía , Decanoatos/administración & dosificación , Humanos , Nandrolona/administración & dosificación , Nandrolona DecanoatoAsunto(s)
Decanoatos/efectos adversos , Ácidos Decanoicos/efectos adversos , Flufenazina/efectos adversos , Heptanoatos/efectos adversos , Ácidos Heptanoicos/efectos adversos , Sistema Nervioso Autónomo/efectos de los fármacos , Ensayos Clínicos como Asunto , Decanoatos/administración & dosificación , Método Doble Ciego , Heptanoatos/administración & dosificación , Humanos , Trastornos del Movimiento/inducido químicamente , Fases del Sueño/efectos de los fármacos , Factores de TiempoAsunto(s)
Decanoatos/sangre , Ácidos Decanoicos/sangre , Flufenazina/sangre , Heptanoatos/sangre , Ácidos Heptanoicos/sangre , Disponibilidad Biológica , Decanoatos/administración & dosificación , Preparaciones de Acción Retardada , Heptanoatos/administración & dosificación , Humanos , Factores de TiempoRESUMEN
Injected intramuscularly, the enanthane and decanoate esters of the phenothiazine fluphenazine are an effective treatment of the disordered behavior and thinking of schizophrenia. The decanoate preparation is not only slightly longer-acting but also has a smaller incidence of side-effects that the enanthate. The major adverse effect of these medications is the high frequency of extrapyramidal system disturbance. Since the 50% rate of failure of schizophrenic outpatients to take prescribed oral medications decreases treatment failure to about 20% with the use of long-acting injectable phenothiazines, this route of administration offers an advantage in patient management particularly applicable to community mental health systems. Moreover, parenteral administration of long-acting fluphenazine may be useful for patients who do not attain effective serum levels with medication taken orally because of metabolic or absorption difficulties.