RESUMEN
AIMS: To develop and evaluate nurse-led discharge criteria for a clinical decision unit in a large NHS Foundation Trust METHOD: Criteria for nurse led discharge were developed for patients presenting to hospital via the emergency department with chest pain, headache and deliberate self poisoning. Data on length of stay on CDU and readmission were collected for these patient groups during a 2 month period, during which the nurse-led criteria were introduced. Following introduction of the criteria a survey was conducted to evaluate staff opinions of the new system. RESULTS: A trend towards reduced length of stay was noted during the month after introduction of nurse-led discharge (18.26 hrs vs 20 hours p=0.582). Our staff survey indicated that the process was popular and has been continued since the study period. CONCLUSION: Nurse-led discharge using defined criteria is feasible and popular with staff in an acute medical setting.
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Dolor en el Pecho/enfermería , Cefalea/enfermería , Evaluación en Enfermería/métodos , Atención de Enfermería/métodos , Alta del Paciente/normas , Intoxicación/enfermería , Desarrollo de Programa , Dolor en el Pecho/terapia , Servicio de Urgencia en Hospital/organización & administración , Femenino , Cefalea/terapia , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Modelos de Enfermería , Intoxicación/terapiaRESUMEN
The present study investigated the safety of induction therapy with daclizumab (compared with no induction treatment), in adult renal transplant patients reported to the Scientific Registry of Transplant Recipients (SRTR) database between January 1, 1998 and July 27, 2003. Patients who were discharged from the hospital on mycophenolate mofetil, azathioprine, or sirolimus were divided into two groups: induction treatment with daclizumab (n = 8203) and no induction treatment (n = 25,368). Patient survival, death due to infection and death due to malignancy were evaluated at 1 and 3 yr post-transplantation. Rejection and graft survival were also examined. Kaplan-Meier and Cox regression models were used to evaluate outcomes. No significant differences were found between patients treated with daclizumab compared with patients who received no induction therapy for death due to infection or malignancy at 1 and 3 yr post-transplantation. Patients treated with daclizumab (compared with no induction treatment) had statistically significantly better survival rates at 1 (96.9% vs. 96.2%, p = 0.003) and 3 yr (92.4% vs. 91.4%, p = 0.004) although absolute differences were minimal. This was confirmed in the multivariable Cox regression analysis for patient death at 1 (HR = 0.77, p < 0.001) and 3 yr (HR = 0.83, p = 0.001) post-transplantation. Patients treated with daclizumab compared to no induction had lower rejection rates at 1 (13.1% vs. 17.3%, p < 0.001) and 3 yr post-transplantation (16.7% vs. 21.3%, p < 0.001). Cox regression confirmed a decreased risk for rejection at 1 (HR = 0.74, p < 0.001) and 3 yr (HR = 0.75, p < 0.001). Treatment with daclizumab was associated with reduced risk for graft loss at 1 (HR = 0.82, p < 0.001) and 3 years (HR = 0.86, p < 0.001). In conclusion, daclizumab was associated with a significantly reduced risk for rejection and graft loss compared with no induction treatment, and improved patient survival. In addition, daclizumab was not associated with an increase in risk of death due to infection or malignancy, when compared with no induction therapy. These findings demonstrate the short and long-term safety and efficacy of daclizumab in patients transplanted between January 1998 and July 2003.
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Anticuerpos Monoclonales/uso terapéutico , Rechazo de Injerto/prevención & control , Inmunoglobulina G/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Adulto , Anticuerpos Monoclonales Humanizados , Daclizumab , Femenino , Humanos , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
BACKGROUND: Sparse published data exist on outcomes in daclizumab-treated cardiac transplant patients. One trial observed an increased mortality risk 6 and 12 months posttransplant in patients receiving daclizumab plus mycophenolate mofetil (MMF), cyclosporine, and steroids. This study further investigates the safety profile of daclizumab with this same immunosuppressive regimen from a large registry. METHODS: Data obtained at hospital discharge on all adult cardiac transplants performed in the USA between January 1998 and October 2003 for patients receiving MMF plus cyclosporine and steroids were accessed from the Scientific Registry of Transplant Recipients. Patients were selected based on induction treatment: daclizumab (n = 684) or no induction (n = 2525). Outcomes were evaluated at 6 months, 12 months, and 3 years posttransplant. Univariate Kaplan-Meier and multivariate Cox models were used to evaluate the effect of treatment on outcomes. Patient survival and infectious death were the primary endpoints. Secondary endpoints included rejection within the first year posttransplant (acute rejection; AR) and total rejection episodes over time. The two treatment groups shared similar demographics and transplant procedure details. RESULTS: Daclizumab (vs no induction) patients had no increased risk of patient death nor infectious death. Daclizumab patients had a lower incidence of AR at 6 months (P = .005) and 12 months (P < .001); the adjusted risk for AR at 12 months (hazards ratio [HR] = 0.77; P = .89) and over 3 years (HR 0.83, P = .006) was also lower in daclizumab-treated patients. CONCLUSIONS: In cardiac transplant patients, daclizumab (vs no induction) does not result in increased mortality or infectious death, and is associated with a lower incidence of AR.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Rechazo de Injerto/prevención & control , Trasplante de Corazón/inmunología , Inmunoglobulina G/uso terapéutico , Inmunosupresores/uso terapéutico , Adulto , Anticuerpos Monoclonales Humanizados , Daclizumab , Quimioterapia Combinada , Femenino , Rechazo de Injerto/epidemiología , Trasplante de Corazón/mortalidad , Humanos , Incidencia , Infecciones/epidemiología , Infecciones/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Complicaciones Posoperatorias/clasificación , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/mortalidad , Sistema de Registros , Análisis de Supervivencia , Factores de Tiempo , Estados UnidosRESUMEN
BACKGROUND: The objective was to evaluate the oedema-protective effect of a vasoactive drug (coumarin/troxerutin [SB-LOT]) plus compression stockings in patients suffering from chronic venous insufficiency after decongestion of the legs as recommended by the new guidelines. PATIENTS AND METHODS: 231 patients were randomly assigned medical compression stockings plus SB-LOT (90 mg coumarin and 540 mg troxerutin per day) or medical compression stockings plus placebo for the first 4 weeks and SB-LOT or placebo for the second 12 weeks of the study. The primary efficacy endpoint was the lower leg volume measured by well-established water plethysmometry. RESULTS: 226 patients were evaluated. After ceasing compression stockings, an edema protective effect was detected in the SB-LOT-group but not in the controls. Recurrence of leg volume increase was by 6.5 +/- 12.1 ml and by 36.7 +/- 12.1 ml in the SB-LOT and placebo group, respectively (p = 0.0402). The local complaint score and general aspects of quality of life were also superior for the SB-LOT-group (p = 0.0041). Significant differences were also observed with regard to clinical global impression and therapeutic effect. No serious adverse drug reaction or clinically relevant impairment of laboratory parameters occur. CONCLUSION: This study confirms the oedema-protective effect of SB-LOT in chronic venous insufficiency and provides a treatment option for patients who discontinue compression after a short time.
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Cumarinas/administración & dosificación , Hidroxietilrutósido/análogos & derivados , Hidroxietilrutósido/administración & dosificación , Insuficiencia Venosa/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Vendajes , Terapia Combinada , Cumarinas/efectos adversos , Preparaciones de Acción Retardada , Método Doble Ciego , Combinación de Medicamentos , Edema/tratamiento farmacológico , Femenino , Humanos , Hidroxietilrutósido/efectos adversos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Gallbladder motor function was studied in nine diabetic patients and nine control subjects matched for sex, age, and weight. None of the subjects had gallstones. Two different techniques were employed: real-time ultrasonography and cholescintigraphy using 99mTc-HIDA as imaging agent. Gallbladder volumes were determined sonographically by using three dimensions: length, lateral, and anterior-posterior diameters. Gallbladder emptying was stimulated by a standard test drink (Biloptin). Ejection fraction was computed and the results obtained by both techniques were compared. Fasting and residual gallbladder volumes after contraction were significantly larger in the diabetic patients than in the control subjects (15.9 +/- 7.6 cm3 vs. 2.3 +/- 1.3 cm3, p less than .0007; and 9.2 +/- 9.8 cm3 vs. 0.7 +/- 0.7 cm3, p less than .0007). Ejection fractions (ultrasonography/cholescintigraphy) were lower in the diabetic patients compared with the control subjects (59.9 +/- 26.6% and 63.1 +/- 23.2% vs. 73.2 +/- 23.8% and 75.3 +/- 24.8%), however, this difference was not statistically significant. Sonographically and scintigraphically determined ejection fractions were closely correlated (r = 0.90, p less than .00005).
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Diabetes Mellitus Tipo 1/fisiopatología , Vesícula Biliar/fisiopatología , Ultrasonografía , Femenino , Vesícula Biliar/diagnóstico por imagen , Humanos , Iminoácidos , Masculino , Persona de Mediana Edad , Compuestos de Organotecnecio , Cintigrafía , Lidofenina de Tecnecio Tc 99mRESUMEN
Serum concentrations of alpha 1-acid glycoprotein (AAG) were studied in six healthy, male volunteers before and after administration of cimetidine, 300 mg by mouth every 6 h for 2 days. Serum AAG concentrations were measured at three different times during the first day, i.e. before cimetidine administration, and on the fourth and sixth days, after commencing cimetidine administration. Neither cimetidine treatment nor time of day contributed significantly to differences in serum AAG concentration, and no interaction of these factors was observed. It is concluded that altered drug-AAG binding as a result of cimetidine therapy is not likely to be an important mechanism contributing to cimetidine drug interactions.
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Cimetidina/farmacología , Orosomucoide/metabolismo , Adulto , Humanos , MasculinoRESUMEN
Solutions of lidocaine hydrochloride are widely used for anesthesia of the oropharynx and respiratory tract prior to endoscopic procedures. It is commonly believed that this route of administration is not associated with clinically significant systemic absorption of the drug, and large doses of topical lidocaine are routinely used in this setting. Serious adverse effects, including seizures, occasionally occur. The extent of absorption of lidocaine from the oropharynx was studied in eight healthy volunteers. Wide variation in serum lidocaine concentrations was observed. A 14-fold range of peak lidocaine concentrations occurred following identical, accurately metered doses of a lidocaine aerosol spray preparation. The effects of cimetidine on lidocaine pharmacokinetics were also studied. Therapeutic doses of oral cimetidine significantly increased the area under the lidocaine time-concentration curve (p = 0.019), but no effect on the terminal-phase elimination rate constant was observed. Serum concentrations of alpha 1-acid glycoprotein, a major binding protein of lidocaine, were significantly elevated following cimetidine (p = 0.030). Maximum lidocaine concentration, time to reach maximum concentration, and mean residence time of lidocaine were unchanged following cimetidine. These observations suggest an effect of cimetidine on the volume of distribution of lidocaine. Because of the wide variability in lidocaine pharmacokinetics and the potentially serious nature of adverse reactions, caution is advised in the use of topical lidocaine solutions in "standard" doses.
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Cimetidina/farmacología , Lidocaína/sangre , Orofaringe/metabolismo , Administración Tópica , Adulto , Interacciones Farmacológicas , Humanos , Orosomucoide/análisisRESUMEN
Almitrine bismesylate is a pharmacologically unique respiratory stimulant. It enhances respiration after both acute and chronic administration by acting as an agonist of peripheral chemoreceptors located on the carotid bodies. In comparison with traditional central-acting respiratory stimulants, almitrine has advantages of oral activity, prolonged duration of effect, and an improved adverse effect profile. Almitrine is generally well tolerated, with headache and minor gastrointestinal disturbances being the most frequently observed side effects. This investigational agent has been shown to increase arterial oxygen tension while decreasing arterial carbon dioxide tension in patients with chronic obstructive pulmonary disease both at rest and during exercise through increased ventilation and improved ventilation/perfusion matching. It may also prove useful in the treatment of nocturnal oxygen desaturation because of its ability to reduce the frequency and severity of nocturnal hypoxemia without impairing the quality of sleep. Additional research is needed to further define the role of almitrine in the relief of hypoxemia.
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Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Piperazinas/uso terapéutico , Insuficiencia Respiratoria/tratamiento farmacológico , Adulto , Anciano , Almitrina , Células Quimiorreceptoras/efectos de los fármacos , Ensayos Clínicos como Asunto , Método Doble Ciego , Humanos , Cinética , Persona de Mediana Edad , Piperazinas/efectos adversos , Piperazinas/metabolismoRESUMEN
Propafenone is a new membrane-stabilizing antiarrhythmic agent that structurally resembles the beta-adrenergic receptor antagonist, propranolol. To determine the potential asthmogenicity of this new drug, pulmonary function, airway reactivity to methacholine, blood pressure, the electrocardiogram, and plasma concentrations were measured in 12 patients with mild intermittent asthma after 48 to 72 hours of treatment with placebo and with oral propafenone in low dosage (150 mg every eight hours) and high dosage (300 mg every eight hours) in a double-blind crossover manner. The forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow over the middle half of the FVC (FEF25-75%), heart rate, and blood pressure during the three regimens of treatment were not significantly different; however, the QRS interval on the ECG was significantly widened with both dosages of active drug, and the mean provocative dose of methacholine (+/- SE) required to reduce FEV1 by 20 percent (PD20) decreased from 3.0 +/- 0.6 mg/ml with placebo to 2.1 +/- 0.7 mg/ml with the high dosage of propafenone (p less than 0.01). The mean PD20 on the low-dose regimen was not significantly different from placebo or high-dose therapy. A potentially relevant increase in airway reactivity, as measured by a ratio of less than 0.5 for PD20 after treatment to PD20 after placebo, occurred in seven subjects with high-dose and in one subject during low-dose treatment (p less than 0.01). These data suggest that propafenone should be used with caution in patients with asthma and that bronchial provocation will provide a more sensitive measure of the asthmogenicity of a drug with beta-adrenergic receptor antagonist activity than pulmonary function tests. Moreover, use of bronchial provocation allows the selection of subjects with mild disease, thus reducing the risk of potentially severe bronchospasm.
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Asma/inducido químicamente , Propafenona/efectos adversos , Adulto , Volumen Espiratorio Forzado , Corazón/efectos de los fármacos , Humanos , Cloruro de Metacolina , Compuestos de Metacolina , Propafenona/sangreRESUMEN
The hypothesis that the cytoprotective agent sucralfate (sucrose octakis(hydrogen sulfate)-aluminum complex) interacts with the H2-antagonist ranitidine (N-[2-[[dimethylamino)methyl]furfuryl]- thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine) by decreasing ranitidine absorption was tested in vitro and in vivo. The in vitro results show that ranitidine may bind to a small extent (approximately 10%) to sucralfate paste in the gastrointestinal fluids. The in vivo ineraction of 150 mg of ranitidine and 1 g of sucralfate was evaluated in a crossover study in six healthy volunteers. The results indicate no significant difference in pharmacokinetic parameters when ranitidine was given alone and in combination with sucralfate. Thus, ranitidine bioavailability is not diminished by sucralfate and the two drugs can be given concomitantly. For the determination of bioavailability, it has to be taken into account that renal clearance of ranitidine is lower after oral than after intravenous administration, and that enterohepatic recirculation of the drug is likely.
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Ranitidina/metabolismo , Sucralfato/metabolismo , Adulto , Cromatografía Líquida de Alta Presión , Interacciones Farmacológicas , Humanos , Absorción Intestinal , Cinética , Masculino , Ranitidina/sangre , Espectrofotometría Ultravioleta , Sucralfato/sangreRESUMEN
Theophylline is a commonly used bronchodilator in the treatment of chronic obstructive airways disease (COAD) with a narrow therapeutic range of 10 to 20 micrograms/ml. Patients with COAD frequently receive concomitant antibiotic therapy for respiratory infections. This study evaluated the effect of tetracycline therapy on theophylline disposition in adults with COAD. Six males (five nonsmokers) with obstructive ventilatory defects were studied in two phases: control, after receiving sustained-release theophylline in the same dosage regimen for four days, and treatment, after receiving tetracycline 250 mg po qid for five days in addition to theophylline. During each phase, 10 blood samples were obtained over one dosing interval and analyzed for theophylline content. The following pharmacokinetic parameters were calculated: Cmin, Cmax, Css, percentage fluctuation and Cl. Differences for each value were tested as paired data with Student's two-tailed t-test. When all patients were evaluated, the only statistically significant difference was for Cmax. However, when the five nonsmokers were evaluated separately, differences were observed for Css (micrograms/ml; mean +/- SD) 9.3 +/- 3.0, control, and 10.6 +/- 3.8, treatment (p = 0.041); and for Cl [( ml/h]/kg; mean +/- SD) 49.0 +/- 11.1, control, and 43.6 +/- 10.2, treatment (p = 0.019). This study demonstrates that tetracycline may weakly inhibit theophylline clearance in nonsmoking adults with COAD.
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Enfermedades Pulmonares Obstructivas/metabolismo , Tetraciclina/farmacología , Teofilina/metabolismo , Adulto , Anciano , Interacciones Farmacológicas , Humanos , Cinética , Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Teofilina/uso terapéuticoRESUMEN
Lactobacillus preparations have been demonstrated to be beneficial in the prevention of antibiotic-associated diarrhea resulting from ampicillin. Since the bioavailability of oral ampicillin is known to be affected by food and fluid volume, a study to evaluate the influence of a lactobacillus product on ampicillin bioavailability was performed. Twelve healthy volunteers, male and female, were studied in a randomized three-way cross-over study. Each received ampicillin alone, ampicillin with a lactobacillus preparation, and ampicillin followed 1 h later by the lactobacillus preparation. Blood was sampled over a 6-h time period. Ampicillin content was determined by high-pressure liquid chromatography. Area under the concentration-time curve, area under the first moment of the concentration-time curve, maximum concentration of drug in plasma, time to maximum concentration of drug in plasma, and mean residence time were determined for each study interval. No differences in maximum concentration of drug in plasma, time to maximum concentration of drug in plasma, area under the concentration-time curve, or mean residence time were seen for either males or females or the combined group. The lactobacillus preparation as used in this study did not appear to interfere with the bioavailability of oral ampicillin.
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Ampicilina/metabolismo , Productos Biológicos/farmacología , Absorción Intestinal/efectos de los fármacos , Administración Oral , Adulto , Ampicilina/sangre , Disponibilidad Biológica , Esquema de Medicación , Femenino , Humanos , Cinética , Masculino , Distribución AleatoriaRESUMEN
This study evaluated the effectiveness of filtering amphotericin B (ampho B) on the incidence and severity of drug-related complications. Fifteen males receiving ampho B via peripheral vein infusion participated in this randomized, double-blind study. Each patient had his dose of ampho B diluted in 500 ml of dextrose 5% in water, to which hydrocortisone 25 mg was admixed and infused over four to six hours. Eight patients had their ampho B infusions filtered through a 1 micron filter after preparation, while seven patients did not have their ampho B infusions filtered. Patients were evaluated daily for phlebitis and selected adverse effects. The two groups were comparable with regard to diagnosis, concomitant drugs, cannula type and size, vein selection, and frequency of iv site change. Four patients in each group developed phlebitis. Statistical testing using the Mann-Whitney U test revealed no difference between groups with regard to patient age, dose of ampho B, frequency and severity of phlebitis, time to onset of initial phlebitis, and frequency of adverse effects (fever, chills, headache, nausea, vomiting, and anorexia). Filtration of ampho B infusions using a 1 micron filter does not appear to decrease the incidence or severity of phlebitis and associated adverse effects.
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Anfotericina B/efectos adversos , Flebitis/prevención & control , Adulto , Anciano , Anfotericina B/administración & dosificación , Ensayos Clínicos como Asunto , Método Doble Ciego , Filtración , Humanos , Infusiones Parenterales , Masculino , Persona de Mediana Edad , Distribución AleatoriaRESUMEN
Lidocaine is absorbed from mucous membranes of the oropharynx, gastrointestinal tract, and tracheobronchial tree. First-pass hepatic metabolism of the drug greatly reduces the amount reaching the general systemic circulation in the normal individual. In patients whose hepatic metabolism is reduced by disease or drugs, or in whom liver blood flow is reduced, this first-pass effect is decreased and lidocaine concentrations may be higher than those produced by the same dose in normal patients. We report an elderly man taking cimetidine with congestive heart failure in whom the accidental ingestion of lidocaine solution for esophageal anesthesia was followed by seizures and elevated serum lidocaine concentrations.
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Anestesia Local/efectos adversos , Esófago , Lidocaína/efectos adversos , Convulsiones/inducido químicamente , Anciano , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Adverse reactions involving the central nervous system have been rarely reported with ranitidine, a H2-receptor antagonist. A 72 year old female is described that developed visual hallucinations shortly after initiation of ranitidine therapy. Rechallenge with the drug resulted in both visual and auditory hallucinations following a single dose.
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Alucinaciones/inducido químicamente , Ranitidina/efectos adversos , Anciano , Úlcera Duodenal/tratamiento farmacológico , Femenino , Humanos , Ranitidina/uso terapéuticoRESUMEN
Research clarifying the role of the parasympathetic nervous system in the pathophysiology of chronic obstructive pulmonary disease (COPD) has renewed interest in anticholinergic therapy of these disease processes. The investigational agent ipratropium bromide produces bronchodilation by competitive inhibition of cholinergic receptors on bronchial smooth muscle, antagonizing the action of acetylcholine. When administered via inhalation at therapeutic doses of 20-40 micrograms, ipratropium is somewhat less effective than beta-agonists in asthmatics. In the treatment of chronic bronchitis, however, ipratropium appears at least as effective as, and possibly superior to, the sympathomimetics. Combination therapy with beta-agonists or theophylline has resulted in enhanced effect over single-agent regimens. Due to the low serum concentrations achieved following inhalation, ipratropium has been well tolerated and is virtually free of significant adverse reactions. The primary role of ipratropium in therapy remains to be defined but appears to be as an alternative to beta-agonists in patients who fail to respond or who experience troublesome side effects. In addition, combination therapy may prove to be another important use of ipratropium in the management of COPD.
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Derivados de Atropina/uso terapéutico , Ipratropio/uso terapéutico , Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Animales , Asma/tratamiento farmacológico , Biotransformación , Bronquitis/tratamiento farmacológico , Fenómenos Químicos , Química , Quimioterapia Combinada , Femenino , Humanos , Absorción Intestinal , Ipratropio/administración & dosificación , Ipratropio/efectos adversos , Ipratropio/metabolismo , Ipratropio/farmacología , Cinética , Embarazo , Distribución TisularRESUMEN
The incidence of dose-dependent pharmacokinetics of theophylline was retrospectively investigated in adults with pulmonary disease receiving continuous aminophylline infusions. Twenty-one of 180 successive admissions to medical intensive care units with a diagnosis of chronic obstructive pulmonary disease, asthma, or respiratory failure met the criteria of two steady-state serum theophylline concentrations on two different doses. Of these, 14 patients continued to smoke, whereas 7 had never smoked or had stopped greater than 1 year prior to admission. No statistical difference existed between the mean systemic clearances of theophylline at the two different doses, using either total body weight or ideal body weight. Only 1 of the 21 patients met the criteria for dose dependency of a greater than or equal to 50% reduction in clearance with dosage increase. Six of eight subjects with decreased clearance on the higher dose were nonsmokers. In contrast, all nine with augmented clearance following dosage increase were smokers. Four were considered to have proportional changes. In general, nonsmoking patients tended to have greater changes in serum theophylline concentration than in dosage. Conversely, smoking patients demonstrated smaller changes in concentration. The relationship of smoking status and dose-dependent theophylline elimination is discussed.
Asunto(s)
Asma/metabolismo , Enfermedades Pulmonares Obstructivas/metabolismo , Teofilina/metabolismo , Adulto , Anciano , Aminofilina/metabolismo , Aminofilina/uso terapéutico , Asma/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Infusiones Parenterales , Cinética , Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Fumar , Teofilina/uso terapéuticoRESUMEN
The accuracy of computer-predicted theophylline serum concentrations compared with actual serum concentrations in patients whose drug therapy was being converted from aminophylline infusions to an oral sustained-release theophylline product (Theo-Dur) was measured. The SIMKIN computer program was used to simulate theophylline serum-concentration curves in nine patients receiving an initial dose of sustained-release theophylline at the time their maintenance aminophylline infusions were discontinued. The sustained-release theophylline doses were calculated using individual patient theophylline clearance values to produce mean theophylline serum concentrations in the normal therapeutic range. Pharmacokinetic variables used in the SIMKIN program were derived from individual patients' serum concentrations and average literature values. Theophylline serum concentrations were measured before the initial dose of the sustained-release product and periodically for 12 hours. Mean SIMKIN-predicted serum theophylline concentrations were within 10% of actual measurements 39% of the time, but data from individual patients varied considerably. Two patients had prolonged absorption lag times that could not be explained. Computer-simulation programs using population-based pharmacokinetic variables to predict theophylline serum concentrations must be tested against in vivo measurements to verify their accuracy.