RESUMEN
We compared oral fluid testing to urine testing in subjects who were administered single doses of marijuana by smoked and oral routes. Oral fluid specimens were collected with the Intercept DOA Oral Specimen Collection Device, screened for THC with the Cannabinoids Intercept MICRO-PLATE Enzyme Immunoassay (EIA) utilizing a 1.0-ng/mL cutoff concentration, and confirmed for THC by gas chromatography-tandem mass spectrometry (GC-MS-MS) with a 0.5-ng/mL cutoff concentration. Urine specimens were screened for 11-nor-carboxy-delta9-tetrahydrocannabinol (THCCOOH) by immunoassay utilizing a 50-ng/mL cutoff concentration and confirmed for THCCOOH by GC-MS with a 15-ng/mL cutoff concentration. Oral fluid specimens tested positive following smoked marijuana (N = 10) consecutively for average periods (+/-SEM; range) of 15 (+/-2; 1-24) and 13 h (+/-3; 1-24) by EIA and GC-MS-MS, respectively. The average THC detection times of the last oral fluid positive specimen following smoked marijuana by EIA and GC-MS-MS were 31 (+/-9; 1-72) and 34 h (+/-11; 1-72), respectively. In comparison to oral fluid, urine specimens generally tested negative for THCCOOH immediately after marijuana use. The average times to detection of the first urine specimen positive for THCCOOH by EIA and GC-MS were 6 (+/-2; 1-16) and 4 h (+/-1; 2-8), respectively. Urine specimens tested positive consecutively for average periods of 26 (+/-9; 2-72) and 33 h (+/-10; 4-72) for EIA and GC-MS, respectively. The average THCCOOH detection times of the last specimen by EIA and GC-MS were 42 (+/-10; 2-72) and 58 h (+/-6; 16-72), respectively. Considering the noninvasive nature of oral fluid collection and improved detection of recent marijuana use compared to urine testing, it was concluded that oral fluid testing for THC offers specific advantages over other means of marijuana testing when used in safety-sensitive testing programs.
Asunto(s)
Abuso de Marihuana/orina , Fumar Marihuana/orina , Saliva/química , Detección de Abuso de Sustancias/métodos , Administración Oral , Adulto , Cromatografía de Gases y Espectrometría de Masas , Humanos , Técnicas para Inmunoenzimas , Masculino , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
The performance characteristics of a method for detecting opiates (morphine, codeine, heroin, and 6-acetylmorphine [6-AM]) in oral fluid specimens were examined and compared with methods for urine specimens. The oral fluid was easily obtained using a simple device that collects between 1 and 1.5 mL of fluid for laboratory analysis. Simultaneously collected specimens from 60 known opiate abusers from a drug-treatment center were first tested using an immunoassay cutoff of 10 ng/mL in oral fluids and 2,000 ng/mL in urine. Using a second aliquot, opiate confirmation in urine was performed by gas chromatography-mass spectrometry (GC-MS) and in oral fluids by GC-MS-MS. The combined immunoassay and GC-MS-MS procedures were completed with less than 250 pL of oral fluid. Opiates identified in oral fluid specimens from heroin users included morphine, codeine, heroin, and 6-AM. The immunoassay was tested for precision, stability, and the effects of potential cross-reactants. The results yielded 93.6% agreement between oral fluid and urine, suggesting that oral fluid may be a reliable matrix for opiate detection.
Asunto(s)
Narcóticos/análisis , Trastornos Relacionados con Opioides/sangre , Trastornos Relacionados con Opioides/orina , Saliva/química , Detección de Abuso de Sustancias/métodos , Codeína/análisis , Codeína/inmunología , Reacciones Cruzadas , Cromatografía de Gases y Espectrometría de Masas , Heroína/análisis , Heroína/inmunología , Humanos , Técnicas para Inmunoenzimas , Morfina/análisis , Morfina/inmunología , Derivados de la Morfina/análisis , Derivados de la Morfina/inmunología , Narcóticos/inmunología , Trastornos Relacionados con Opioides/diagnóstico , Papaver/inmunología , Reproducibilidad de los Resultados , Semillas/inmunología , Sensibilidad y Especificidad , Relación Estructura-Actividad , Detección de Abuso de Sustancias/instrumentaciónRESUMEN
The treatment of cytomegalovirus retinitis has during the last years been done mainly with sustained release ganciclovir devices implanted in the vitreous. In the present study it is shown that ganciclovir can be administered into the rabbit vitreous by microdialysis. A concentration of about 10(-6) M, which is considered within the therapeutic range, is achieved in the vitreous after a microdialysis perfusion. The method offers possibility of variation in the drug delivery that is not possible with the ganciclovir implants.
Asunto(s)
Antivirales/administración & dosificación , Retinitis por Citomegalovirus/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Ganciclovir/administración & dosificación , Microdiálisis , Animales , Antivirales/farmacocinética , Retinitis por Citomegalovirus/metabolismo , Modelos Animales de Enfermedad , Implantes de Medicamentos , Ganciclovir/farmacocinética , Conejos , Cuerpo Vítreo/metabolismoRESUMEN
PURPOSE: Microdialysis has been used in eye research for almost a decade. We have previously developed and used it mainly for chronic experiments and here it is used in acute experiments. It is highly suitable for both administration and withdrawal of substances from the eye, as it only permits molecules to cross the intraocular membrane without any net fluid movement in or out of the eye. METHODS: We have here investigated the ability of 125I labeled NGF (nerve growth factor) to cross a previously implanted high permeability membrane of a new type (polyether sulphone, PES, cutoff at 100000 daltons) in the rabbit vitreous. It was perfused for different time periods with a solution containing NGF The radioactivity of the entire vitreous was then counted. RESULTS: The results show detectable levels (up to 10(-11)M) of the substance after the perfusions. CONCLUSION: We conclude that microdialysis with PES membranes is a possible method for the intraocular administration of NGF.
Asunto(s)
Microdiálisis/métodos , Factor de Crecimiento Nervioso/administración & dosificación , Factor de Crecimiento Nervioso/farmacocinética , Cuerpo Vítreo/metabolismo , Animales , Membranas Artificiales , Polímeros , Conejos , SulfonasRESUMEN
The method of microdialysis was used for collecting series of samples from the rabbit vitreous after systemic and intravitreous administration of ceftazidime. The purpose of the study was to compare the method with traditional pharmacokinetic sampling. Ceftazidime was injected intramuscularly (1 mg/kg) or intravitreally (1 mg) in rabbits, with a previously implanted microdialysis probe in the vitreous. The membrane was perfused with a buffer, and the dialysate was collected in samples where the concentration of the drug was analyzed by HPLC. After intramuscular administration, blood samples were taken to calculate systemic pharmacokinetics. The same procedures were repeated with rabbits with mild intraocular inflammation induced by the injection of 400 EU of endotoxin into the vitreous, 12-15 hr before drug administration. Pharmacokinetic parameters, such as half-life and AUC, were calculated. The penetration into the vitreous after intramuscular injection was higher (42%) in inflamed than in non-inflamed eyes (20%), suggesting an interference with the blood retinal barrier. Other kinetic parameters did not differ significantly between the groups. The advantage of the method is that fewer experimental animals can be used to obtain the necessary data compared to traditional pharmacokinetic methods. In conclusion, intraocular dialysis with chronically implanted probes is a technique well suited for pharmacokinetic studies of systemically administered ceftazidime or other drugs that will pass a dialysis membrane.
Asunto(s)
Ceftazidima/farmacocinética , Inflamación/metabolismo , Cuerpo Vítreo/metabolismo , Administración Tópica , Animales , Ceftazidima/sangre , Cromatografía Líquida de Alta Presión , Endotoxinas , Femenino , Masculino , Microdiálisis , ConejosRESUMEN
Intraocular microdialysis was used to administer the drugs 5-fluorouracil, benzyl penicillin, daunomycin and dexamethasone into the vitreal space of rabbits. The purpose of the study was to investigate if therapeutic concentrations could be obtained with this administration method. After administering the drugs in labelled form, the attained concentrations were assessed by counting the radioactivity in the entire vitreous. For benzyl penicillin, the concentration was 2 microM, for dexamethasone it was 1.2 x 10(-7) M, and for daunomycin it was 1.2 microM, which are considered to be within the therapeutic ranges. For 5-fluorouracil, the corresponding concentration was 5 x 10(-5) M which probably is below the therapeutic level, when comparing with single-dose injections.
Asunto(s)
Antibacterianos/farmacocinética , Antimetabolitos/farmacocinética , Dexametasona/farmacocinética , Fluorouracilo/farmacocinética , Glucocorticoides/farmacocinética , Cuerpo Vítreo/metabolismo , Animales , Disponibilidad Biológica , Daunorrubicina/farmacocinética , Femenino , Masculino , Membranas Artificiales , Microdiálisis/métodos , Penicilina G/farmacocinética , ConejosRESUMEN
BACKGROUND: Since drug penetration from the blood to the vitreous body is very poor, it is important to find means other than systemic delivery to reach necessary intraocular concentrations of drugs. This study represents a step in this direction. METHOD: Microdialysis probes implanted intraocularly in rabbits were perfused with different substances, mainly drugs. The substances belonged to three groups, antibiotics, corticosteroids and cytostatics, and were: benzylpenicillin and cefuroxim; triamcinolone and dexamethasone; daunomycin and 5-fluorouracil. In addition, three substances of different molecular weights were tested: formic acid (MW 70), glucose (MW 189) and insulin (MW ca. 5200). RESULTS: When used in tracer concentrations, some lipophilic drugs stick to polycarbonate but not to polyamide membranes. The latter material has therefore been used in all intraocular perfusions. All substances except inulin were found to diffuse through the polyamide membrane into the vitreous at a rate of about 10-20% of the perfusate concentration. Membranes with different dimensions and the above-mentioned two materials have also been screened for their transport properties in vitro. No differences were found between the two membrane materials, polycarbonate and polyamide. The net dialysis is strongly dependent on the probe geometry. CONCLUSIONS: We have shown that the above-mentioned substances penetrate into the vitreous body of rabbits through an implanted microdialysis membrane. This is of importance for the development of new means of intraocular drug administration.
Asunto(s)
Antibacterianos/farmacocinética , Antineoplásicos/farmacocinética , Glucocorticoides/farmacocinética , Membranas Artificiales , Microdiálisis , Animales , Difusión , Sistemas de Liberación de Medicamentos , Perfusión , Conejos , Retina/metabolismo , Retina/patología , Distribución Tisular , Cuerpo Vítreo/metabolismo , Cuerpo Vítreo/patologíaRESUMEN
The technique of microdialysis in vivo, much used in brain experiments, has been adapted for intraocular use. A new probe was designed, made from a soft tube with the dialysis membrane mounted in a fenestrated protecting sleeve, facing one side. A special surgical procedure was developed for the long-term implantation of the probes. They stay functional in the eyes for several weeks or more. Previously published intraocular microdialysis studies were short-term experiments. The acute surgical trauma is likely to affect the concentration of many compounds in the vitreous, and this effect is minimized with long-term probes.
Asunto(s)
Diálisis/métodos , Cuerpo Vítreo/metabolismo , Aminoácidos/análisis , Animales , Diálisis/instrumentación , Soluciones para Diálisis/análisis , Diseño de Equipo , Ojo/metabolismo , Ojo/patología , Perfusión , ConejosRESUMEN
The ability of certain neuropeptides (glucagon, somatostatin, leu-enkephalin and neurotensin) to release known neurotransmitters (glycine, GABA, dopamine and 5-hydroxytryptamine) was tested in the chicken retina. Tritiated neurotransmitters were injected intravitreally in chicken eyes. After excision, the retina was stimulated in vitro with the neuropeptide in micromolar concentrations while monitoring the efflux of radioactivity from the retina. A rise of the efflux represents a stimulus dependent release. Neurotensin release [3H] glycine, [3H]dopamine and [3H]5-hydroxytryptamine. Leu-enkephalin released [3H]dopamine and somatostatin released [3H]5-hydroxytryptamine. Glucagon was without effect. [3H]GABA was not released by any of the neuropeptides.