Mathematical modelling of in situ and in vitro efflux of ciprofloxacin and grepafloxacin.

The efflux process due to p-glycoprotein-like mechanisms of ciprofloxacin (CIP) and grepafloxacin (GRX) has been studied "in situ" in rats and "in vitro" in Caco-2 cells. The results were modelled by a curve fitting procedure which allowed the characterization of the passive (Pd) and carrier mediated parameters (Vm and Km) from the raw data without initial velocities estimation. CIP absorption in rat was characterized as a passive diffusion at the assayed concentrations. Although the involvement of an efflux transporter cannot be ruled out, its relevance in the transport of the fluoroquinolone is negligible. In GRX absorption, an efflux process is implicated and it is detected in both absorption models. GRX permeability depends on the intestinal segment, reflecting the previously reported different expression level of the efflux transporters along the gut in rat. A first attempt to correlate the "in vitro" and the "in situ" data has been done. The mathematical model has been constructed using very simplistic assumptions and it will require further refinement but, nevertheless, the results are promising and demonstrate that a good modelling approach helps to identify the system critical parameters and how the system behaviour change when the parameters are modified as it happens when we move from the "in vitro" to the "in situ" level. Predicted versus experimental permeability values show a good correlation, demonstrating that the relevance of the secretion process "in situ" in rat can be predicted from the "in vitro" cell results.

Kinetic modeling of triamterene intestinal absorption and its inhibition by folic acid and methotrexate.

The aim of this work was to study the intestinal absorption process of triamterene in situ in rats in order to gain insight on its absorption mechanism. The study shows an example of application of a pharmacokinetic model for drug disappearance from a compartment by simultaneous first order and Michaelis-Menten processes to the intestinal drug disappearance by absorption in a non-steady state system. The parameter used to quantify absorption was the absorption rate constant, determined in situ by means of a loop perfusion technique, performed in colon and in whole small intestine of rat at three pHs (5.00, 7.00 and 8.00) and in the presence of folic acid and methotrexate. Different concentrations of the drug were perfused in each condition. The concentrations versus time data were modeled with different kinetic absorption and inhibition differential equations to obtain the passive and active transport components and to elucidate the inhibition mechanisms. The results obtained confirm that triamterene is absorbed by means of passive diffusion and by a transporter or transporters related to folates. Folic acid and methotrexate are able to inhibit triamterene absorption. The results do not allow the selection of a competitive or non-competitive model for inhibition and this fact could be due to the presence of different carriers. The possibility of the existence of a secretion process sensitive to verapamil is also discussed.

[A version of DSM-IV criteria adapted for adolescents and applied to young smokers]. / Aplicación en jóvenes fumadores de una versión de los criterios nosológicos DSM-IV adaptada para adolescentes.

OBJECTIVES: To evaluate nicotine dependence in adolescent smokers using a version of DSM-IV criteria for nicotine dependence adapted for adolescents (DSM-IVa). To establish its usefulness and the most relevant items for diagnosing adolescent smokers. POPULATION AND METHODS: Two thousand six hundred forty-seven schoolchildren between 10 and 17 years old were surveyed. A sample size was calculated for each year of age, using the finite population equation with the addition of 10% so that the absolute error would not increase at the end of the study if questionnaires were withdrawn. The sample was stratified by sex and type of school for each age group, with allocation to each stratum proportional to the number of individuals. Schools and students were selected using random number tables. The questionnaire collected the most significant personal data and information related to DSM-IVa criteria. RESULTS: Smokers made up 23.1% of the sample, and 63.5% of them smoked daily. According to the DSM-IVa criteria, 70.7% of the smokers were nicotine dependent. The DSM-IVa had a kappa value of 1 and internal consistency was good (Cronbach's alpha: 0.5598). CONCLUSIONS: The DSM-IVa is useful in the studied population, although not perfect. According to the criteria, 70.7% of those interviewed were already nicotine dependent. The key questions were those that referred to the presence of nicotine withdrawal syndrome symptoms and the need to spend a large amount of free time obtaining or smoking cigarettes.

Aplicación en jóvenes fumadores de una versiónde los criterios nosológicos DSM-IV adaptadapara adolescentes / A version of DSM-IV criteria adapted for adolescents and applied to young smokers

OBJETIVOS: Valorar la dependencia nicotínica en jóvenes fumadores a través de una versión adaptada para adolescentes de los criterios nosológicos DSM-IV para la dependencia a la nicotina (DSM-IVa). Determinar su utilidad y los ítems más importantes del mismo en adolescentes fumadores. POBLACIÓN Y MÉTODOS: Se entrevistó a 2.647 escolares de entre 10 y 17 años. Se calculó un tamaño muestral para cada edad, en años, mediante la ecuación de poblaciones finitas, añadiendo un 10 por ciento para que en el caso de existir mermas no aumentasen el error absoluto final. Para cada edad el muestreo fue estratificado por sexo y tipo de centro, con afijación en cada estrato proporcional al número de individuos. La elección de centros y alumnos se hizo mediante tabla de números aleatorios. La encuesta, además de recoger los principales datos personales, comprendía una versión adaptada a adolescentes de los criterios nosológicos DSM-IV para la dependencia a la nicotina. RESULTADOS: El 23,1 por ciento eran fumadores, y de ellos el 63,5 por ciento eran fumadores diarios. Según el DSM-IVa, el 70,7 por ciento de los fumadores eran dependientes de la nicotina. El DSMIVa obtuvo un índice kappa de 1 y una buena consistencia interna (coeficiente alfa de Cronbach = 0,5598). CONCLUSIONES: El DSM-IVa es útil en dicha población, aunque no perfecto. Según sus criterios, el 70,7 por ciento de los entrevistados ya se habían vuelto dependientes de la nicotina, siendo las preguntas clave las referentes a la presencia de síntomas del síndrome de abstinencia nicotínica y a la necesidad de emplear gran parte del tiempo libre en conseguir o consumir tabaco (AU)

Transintestinal secretion of ciprofloxacin, grepafloxacin and sparfloxacin: in vitro and in situ inhibition studies.

The influence of the secretion process on the absorption of ciprofloxacin, grepafloxacin and sparfloxacin has been evaluated by means of inhibition studies. Two well known P-glycoprotein inhibitors (cyclosporine, verapamil), a mixed inhibitor of P-glycoprotein and the organic cation transporter OCT1 (quinidine) and a well established MRP substrate (p-aminohipuric acid) have been selected in order to distinguish the possible carriers implicated. An in situ rat gut perfusion model and CACO-2 permeability studies are used. Both methods suggest the involvement of several types of efflux transporters for every fluoroquinolone. The relevance of the secretory pathway depends on the intrinsic permeability of the quinolone. The in vitro model seems to be more suitable for discriminating mechanisms underlying the absorption process, while in situ studies are less sensitive to inhibition studies.

[Anti-smoking specialist medical prescription or medical counseling in primary care: opinions from the other side of the table]. / Prescripción facultativa o consejo médico antitabaco en atención primaria: opiniones desde el otro lado de la mesa.

OBJECTIVES: To estimate the frequency, characteristics and follow-up of anti-smoking counseling given to patients using a primary care facility; to survey patient opinion of anti-smoking advice offered. MATERIAL AND METHODS: Cross-sectional, descriptive study at a primary care facility. SUBJECTS: random sample of 330 patients between 15 and 75 years of age using the primary care facility in March and April 2000. MEASUREMENTS: confidential survey by self-administered questionnaire on smoking, chronic disease related to smoking, anti-smoking advice given and patient opinion of anti-smoking counseling by health care givers. RESULTS: The prevalence of smoking was 31.9% (100). Among patients who were either smokers or ex-smokers (162), advice to stop smoking had been received from the primary care physician by 47 patients (29.2%), from a specialist by 19 (11.8%), from a nurse by 14 (8.7%), from a pharmacist by 5 (3.1%), and from family by 34 (21.1%). We found no statistically significant differences related to gender or age for advice to stop smoking, although the presence or absence of chronic disease did affect counseling. Fifty-four (65%) of those who had been advised to quit considered that the time spent counseling was adequate. Ten patients (12%) received an informative brochure in addition to counseling. Forty smokers (40%) stated that they would quit smoking if their doctor advised them to and 45 (45%) would do so if they had a smoking-related disease. Thirty-three smokers (33%) believed that they should receive advice about smoking at all visits to the doctor, whereas 38 (38%) believed such counseling was appropriate only if the visit was for a smoking-related disease. CONCLUSIONS: The prevalence of smoking among patients who use primary care facilities is high. The frequency of advice to quit smoking is low, and reminders and follow-up are minimal. After learning a patient's habits and studying them, professional anti-smoking advice should always be given, with appropriate monitoring and follow-up.

Prescripción facultativa o consejo médico antitabaco en atención primaria: opiniones desde el otro lado de la mesa / Specialist medical prescription or medical counseling in primary care: opinions from the other side of the table

OBJETIVOS: Conocer la frecuencia, las características y el seguimiento de la prescripción sanitaria antitabaco en los pacientes que acuden a las consultas de atención primaria (AP); valorar la opinión de los pacientes sobre el consejo sanitario antitabaco recibido. MATERIAL Y MÉTODOS: Estudio descriptivo transversal realizado en AP. Sujetos: muestra aleatoria de 330 pacientes entre 15 y 75 años que acudieron a las consultas de AP durante los meses de marzo y abril de 2000. Mediciones: encuesta confidencial autoadministrada sobre hábito tabáquico, enfermedades crónicas relacionadas con el tabaco, prescripción sanitaria antitabaco recibida y opinión sobre el consejo sanitario antitabaco. RESULTADOS: La prevalencia de fumadores era del 31,9 por ciento (100). Considerando el conjunto de fumadores y ex fumadores (162), el 29,2 por ciento (47) recibió consejo antitabaco del médico de AP, 11,8 por ciento (19) del especialista, el 8,7 por ciento (14) del personal de enfermería, el 3,1 por ciento (5) del farmacéutico y el 21,1 por ciento (34) de la familia. No se encontró una relación estadísticamente significativa entre la prescripción sanitaria antitabaco y el sexo o la edad, pero sí con la presencia de una enfermedad crónica. El 65 por ciento (54) de las personas que habían recibido consejo antitabaco consideraron que el tiempo empleado en dicho consejo fue adecuado. En el 12 por ciento (10) de las ocasiones, además del consejo, se entregó un folleto informativo. El 40 por ciento de los fumadores refiere que dejaría de fumar si su médico se lo aconsejase, y el 45 por ciento lo haría si tuviese una enfermedad relacionada con el tabaco. El 33 por ciento de los fumadores opina que debe recibir prescripción sanitaria antitabaco en todas las consultas, mientras que el 38 por ciento sólo si tuviera una enfermedad relacionada con el tabaco. CONCLUSIONES: La prevalencia de fumadores que acuden a las consultas de AP es elevada. La prescripción sanitaria antitabaco es baja, su recuerdo y seguimiento son mínimos. Tras averiguar el hábito del paciente y estudiarlo, siempre efectuaremos una prescripción facultativa antitabaco, asesorando y realizando el seguimiento oportuno (AU)

Evaluación de la calidad de comunicación entre niveles asistenciales mediante el documento interconsulta / Evaluation of the quality of communication between care levels through the inter-consultation document

Objetivos. Evaluar la calidad y mejora de cumplimentación de los documentos de interconsulta en el equipo de atención primaria (EAP). Diseño. Ciclo completo de calidad. Emplazamiento. Atención primaria (AP).Componentes de la evaluación. Dimensión estudiada: calidad científico-técnica. Sujetos: todos los documentos de interconsulta (DI-1) dirigidos por los médicos de AP del centro de salud de Irún Centro a atención especializada durante 15 días, 223 DI-1 para la evaluación en abril de 1998 y 287 para la reevaluación en octubre 1998. Tipo de evaluación: retrospectiva. Fuente de datos: documentos interconsulta e historias clínicas. Criterios: explícitos y normativos. Medidas correctoras: educativas (discusión de resultados en reunión del EAP).Resultados. En la reevaluación se observó una mejoría estadísticamente significativa: datos de filiación (91,5-96,8 por ciento), legibilidad (86-92,7 por ciento), antecedentes y/o medicación habitual (35,9-50 por ciento) y sintomatología (77,8-87,2 por ciento). Por niveles de calidad se ha pasado en los buenos del 20,6 al 42,5 por ciento y en los malos del 40,8 al 33,4 por ciento. Obtuvimos respuesta en un 22,2 por ciento de nuestras derivaciones. La falta de respuesta se produce en un 34 por ciento por no haber informe del especialista, un 47,8 por ciento se atribuyen al paciente o al circuito y el 18 por ciento de los pacientes está pendiente de pruebas. Conclusiones. La información proporcionada en los DI-1 ha mejorado significativamente después del ciclo de calidad. Conocer nuestra práctica habitual de trabajo sirve como estimulo de mejora. Los criterios que peor cumplimos son: referencia a antecedentes personales y/o medicación habitual, exploración física y medidas terapéuticas empleadas. Gran perdida de información en la respuesta a nuestras derivaciones (AU)

[Evaluation of the quality of communication between levels of care through the inter-consultation document]. / Evaluación de la calidad de comunicación entre niveles asistenciales mediante el documento interconsulta.

OBJECTIVES: To evaluate the quality and improvement of compliance in the inter-consultation documents of the primary care team (PCT). DESIGN: Entire care cycle. SETTING: Primary care (PC). MEASUREMENTS: Dimension studied: scientific-technical quality. SUBJECTS: all the inter-consultation documents (ID-1) sent by PC doctors from Irun Health Centre to specialist clinics over a 15-day period. 223 ID-1 for evaluation in April 1998, and 287 for re-evaluation in October 1998. Type of evaluation: retrospective. SOURCE OF DATA: inter-consultation documents and clinical records. CRITERIA: explicit and standard. Corrective measures: educational (discussion of results in meeting of the PCT). RESULTS: A statistically significant improvement was found at the re-evaluation: basic personal details (91.5%-96.8%), legibility (86%-92.7%), medical history and/or customary medication (35.9%-50%) and symptoms (77.8%-87.2%). Good quality levels rose from 20.6% to 42.5%; and bad quality levels fell from 40.8% to 33.4%. 22.2% of our referrals received a reply. 34% of the lack of replies was because of no report from the specialist, 47.8% were attributed to the patient or circuit, and 18% of the patients were awaiting test results. CONCLUSIONS: The information supplied in the ID-1 improved significantly after the quality cycle. Knowing our habitual working practice can serve to stimulate improvement. The criteria we complied with least were: reference to personal antecedents and/or habitual medication, physical examination, and therapeutic measures employed. There was a huge loss of information in the replies to our referrals.