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OBJECTIVE: This study had three purposes: first, to explore differences in fetal cardiac function in patients with and without intrahepatic cholestasis of pregnancy (ICP) based on PR interval (the interval between the beginning of the atrial contraction and the beginning of the ventricular contraction). Second, to explore a potential correlation between PR interval and bile acid levels in pregnant women with ICP. Third, to study changes in PR interval of fetuses from pregnant women with ICP after administration of ursodeoxycholic acid (UDCA). STUDY DESIGN: This was a prospective observational case-control study. ICP was defined as palmar plantar pruritus of nocturnal predominance for more than 1 week associated with a total bile acid level >10 µmol/L. Control cases were women with pregnancies scheduled for induction or elective cesarean section at term. RESULTS: One hundred and ten women with ICP and 72 controls were included in the study. Median gestational age at inclusion was 35.9 weeks. Median PR interval was significantly longer in fetuses of women with ICP (122 vs. 102 ms, p < 0.001). There was a significant correlation between bile acid levels and PR interval (rho = 0.723, p < 0.001). In 22 fetuses, the median PR interval decreased significantly following UDCA administration (134 vs. 118 ms, p = 0.004). CONCLUSION: PR interval is longer in fetuses of women with ICP. PR interval was significantly correlated with bile acid levels, and administration of UDCA significantly reduced PR interval. KEY POINTS: · Differences in fetal cardiac function in patients with and without intrahepatic cholestasis.. · PR interval and bile acid levels in pregnant women with intrahepatic cholestasis.. · Changes in PR interval of fetuses from pregnant women with ICP after use of UDCA..

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Preeclampsia is a pregnancy-specific disorder defined by new onset of hypertension and proteinuria after 20 weeks of gestation. The early detection of patients at risk of developing preeclampsia is crucial, however, predictive models are still controversial. We aim to evaluate the diagnostic performance of a predictive algorithm in the first trimester of pregnancy, in order to identify patients that will subsequently develop preeclampsia, and to study the effect of aspirin on reducing the rate of this complication in patients classified as high risk by this algorithm. A retrospective cohort including 1132 patients attending prenatal care at Clínica Dávila in Santiago, Chile, was conceived. The risk of developing preeclampsia (early and late onset) was calculated using algorithms previously described by Plasencia et al. Patients classified as high risk, in the first trimester of pregnancy, by these algorithms, were candidates to receive 100 mg/daily aspirin as prophylaxis at the discretion of the attending physician. The overall incidence of preeclampsia in this cohort was 3.5% (40/1132), and the model for early onset preeclampsia prediction detected 33% of patients with early onset preeclampsia. Among the 105 patients considered at high risk of developing preeclampsia, 56 received aspirin and 49 patients did not. Among those who received aspirin, 12% (7/56) developed preeclampsia, which is equal to the rate of preeclampsia (12% (6/49)) of those who did not receive this medication. Therefore, the diagnostic performance of an algorithm combining uterine artery Doppler and maternal factors in the first trimester predicted only one third of patients that developed preeclampsia. Among those considered at high risk for developing the disease using this algorithm, aspirin did not change the incidence of preeclampsia, however, this could be due either to the small study sample size or the type of the study, a retrospective, non-interventional cohort study.

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Purpose: The aim of this study was to compare the bioavailability of two formulations of metformin 850 mg tablets: Glucophage® from Merck Santè laboratories (reference product) and Metformin from Winthrop Pharmaceuticals de Colombia SA (test product) in healthy Colombian volunteers.Methods: A random, double blind, two-period, two-week wash out period, crossover study was performed in 24 healthy male and female volunteers for a single 850-mg dose of metformin tablets administrated with 240 ml of water after 12 hours of fasting. Once the drug was administrated, blood samples were collected before and within 24 hour, and plasma metformin concentration was determined by using a validated HPLC method. Pharmacokinetic parameters such as Cmax, AUC0-96h, AUC0-∞, and Tmax were determined. The formulations were considered bioequivalent if the logarithmic mean ratios of ln-transformed Cmax and AUC0-∞ values were within the equivalence range of 80%-125%.Results: ANOVA analysis of the ln-transformed Cmax and AUC0-∞ indicated that none of the effects examined (formulation, period, within and between-subjet variances and carry over) was statistically significant. The mean (±SD) of Cmax 1217.38 (± 251.72) ng/ml vs. 1305.25 (± 301.06) ng/ml, AUC0-96h 1363.49 (± 315.51) ng.h/ml vs. 1584.82 (± 368.75) ng.h/ml, AUC0-∞, 7155.75 (± 1440.74) ng.h/ml vs. 7777.08 (± 1896.49) ng.h/ml, and Tmax 2.57 (± 0.93) h vs. 2.22 (± 0.94) h were obtained with test and reference formulations, respectively. These pharmacokinetic parameters presented differences with the results from other published papers. The 90% confidence interval of the logarithmic ratio of AUC0-∞ and Cmax was within the range of 80-125%.Conclusions: In this study in healthy Colombian volunteers, a single 850-mg dose of metformin tablet test formulation met the criteria for bioequivalence to the reference formulation based on pharmacokinetic parameters AUC0-∞ and Cmax.

Objetivo: El objetivo de este estudio es comparar la bioequivalencia de dos formulaciones de tabletas de metformina de 850 mg: Glucophage® del Laboratorio Merck Santè (producto de referencia) y metformina de Laboratorios Winthrop Pharmaceuticals de Colombia SA (producto de prueba), en voluntarios colombianos sanos.Métodos: Se realizó un estudio aleatorizado, doble ciego, cruzado, en dos períodos y con un tiempo de lavado de dos semanas, en 24 voluntarios sanos, hombres y mujeres, que recibieron una dosis única de metformina de 850 mg, con 240 ml de agua, después de 12 horas de ayuno. Luego de la administración del medicamento, se recolectaron muestras de sangre durante 24 horas y las concentraciones plasmáticas de metformina se determinaron con un método de HPLC validado. Se calcularon los parámetros farmacocinéticos: Cmax, AUC0-96h, AUC0-∞, y Tmax. Las formulaciones se consideraron bioequivalentes si la relación de la media transformada a ln de Cmax y AUC0-∞ estaba dentro del rango de bioequivalencia de 80% a 125%.Resultados: El Anova de los datos transformados a ln de Cmax y AUC0-∞ indicaron que ninguno de los efectos analizados (formulación, período, variación intra e intersujetos y arrastre) fueron estadísticamente significativos. La media (±SD) de los parámetros obtenidos para los productos de prueba y de referencia, respectivamente, fueron: Cmax 1217.38 (± 251.72) ng/ml vs. 1305.25 (± 301.06) ng/ml, AUC0-96h 1363.49 (± 315.51) ng.h/ml vs. 1584.82 (± 368.75) ng.h/ml, AUC0-∞, 7155.75 (± 1440.74) ng.h/ml vs. 7777.08 (± 1896.49) ng.h/ml, and Tmax 2.57 (± 0.93) h vs. 2.22 (± 0.94) h. El intervalo de confianza de la relación logarítmica del AUC0∞ y Cmax se encontró dentro del rango de 80% a 125%.

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Las enfermedades cardiovasculares son la primera causa de muerte a nivel mundial y en América Latina. El estudio INTERHEART es un estudio diseñado para comparar la importancia de los diferentes factores de riesgo de Infarto del Miocardio a nivel mundial. Material y Método: es un estudio de casos incidentes y controles realizado en 52 países. Los casos eran pacientes que ingresaron con un primer Infarto y los controles fueron pareados por sexo, edad y centro. En ambos grupos se determinó datos demográficos, nivel socioeconómico, estilo de vida, factores psicosociales, historia personal y familiar de enfermedad cardiovascular y factores de riesgo. Se midió índice cintura cadera y Apolipoproteina B y ApoA1. Resultados: A nivel mundial la asociación más fuerte ocurrió con tabaquismo actual (OR 2,87) y relación ApoB/ApoA1 elevada (OR 3,25, quintil superior vs inferior), seguida de factores psicosociales (OR 2,67), historia de diabetes (OR 2,37) e historia de hipertensión (OR 1,91). En América Latina los factores más prevalentes fueron obesidad abdominal, tabaquismo y niveles de ApoB/ApoA1 en el tercil superior. La asociación más fuerte con OR de 2,81 correspondió a historia de hipertensión arterial y a estrés permanente. El consumo diario de frutas y/o verduras y el ejercicio regular tuvieron un efecto protector similar con OR 0,63 (0,51-0,78) y 0,67 (0,55-0,82). El mayor riesgo atribuible poblacional, se debió a obesidad abdominal: 45,8% (35,8-56,2), niveles elevados de Apo B/ApoA1: 40,8 % (30,3-52,2) y tabaquismo: 38.4% (32,8-44,4). En América Latina y el mundo esto factores explican aproximadamente el 90% de los infartos. Conclusión: Los factores de riesgo conocidos permiten explicar casi la totalidad del riesgo de infarto del miocardio a nivel mundial y en América Latina. Su control tendrá un impacto significativo en el control de esta enfermedad...

Cardiovascular diseases are the main cause of death in the world and Latin America. The INTERHEART study was designed to assess the importance of different risk factors for myocardial infarction worldwide. Material and Methods: this is an incident case and control study performed in 52 countries. Cases were patients admitted with a first myocardial infarction. Controls were paired by gender, age and center. In both group demographic data, socioeconomic status, lifestyle, psychosocial factors, personal and family medical cardiovascular story and risk factors were determined. Waist to hip ratio and Apolipoprotein B and ApoA1 were measured. Results: worldwide the strong association was with active smoking (OR 2,87) and increased ApoB/ApoA1 ratio (OR 3,25, upper vs. lower quintile), followed by psychosocial factors (OR 2,67), history of diabetes (OR 2,37) and history of hypertension (OR 1,91). In Latin America the highest prevalence was for abdominal obesity, smoking and ApoB/ApoA1 in the upper tertile. The stronger association was with history of hypertension and permanent stress (OR 2,81. Daily fruit and vegetables consumption and exercise had a similar protective effect, OR 0,63 (0,51-0,78) and 0,67 (0,55-0,82) respectively. The highest population attributable risk was due to abdominal obesity 45.8% (35,8-56,2), increased levels of Apo B/ApoA1 ration: 40,8 % (30,3-52,2) and smoking: 38,4% (32,8-44,4). In Latin America and the rest of the World these factors explained approximately 90% of the myocardial infarctions. Conclusion: known risk factors can explain almost all the myocardial infarction risk in the World and in Latin America. Risk factor control may have a significant impact in the myocardial infarction impact worldwide...

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Con el fin de determinar la bioequivalencia de dos formulaciones de tabletas de 2 mg de clonazepam: Sedatril®/Clonazepam MK (Tecnoquímicas S. A., Cali, Colombia) como producto de prueba y Rivotril® (Roche Químicos e Farmacéuticas S. A., Río de Janeiro, Brasil), como producto de referencia, se realizó un estudio de bioequivalencia en 26 voluntarios sanos. Los productos de prueba y de referencia se administraron en condiciones de ayuno de acuerdo con un diseño cruzado aleatorio de dosis única, con dos secuencias, dos tratamientos y un período de lavado de 28 días. Las muestras de sangre se obtuvieron desde las 0 hasta las 96 horas después de la administración del medicamento. Los niveles plasmáticos de clonazepam se determinaron con un método validado por cromatografía líquida de alta eficiencia con detección ultravioleta (HPLC/UV, siglas en inglés). Los parámetros farmacocinéticos ABC0-96, ABC0-∞, Cmax, Tmax, t1/2, and ke se determinaron de los perfiles plasmáticos concentración-tiempo por el método no compartimental. El test de bioequivalencia se realizó con los datos transformados a logaritmo natural (ln) de ABC0-∞ and Cmax. Los intervalos de confianza del 90 por ciento para la relación producto de prueba/producto de referencia fueron de 87,9 por ciento a 103,6 por ciento y 84,4 por ciento a 104,0 por ciento, respectivamente. Estos resultados estuvieron dentro de los rangos de aceptación del 80,0 por ciento al 125 por ciento, establecidos por la FDA y se concluyó que ambos productos son bioequivalentes.

In order to determine the bioequivalence of two formulations of clonazepam 2 mg tablets: Sedatril®/ Clonazepam MK (Tecnoquímicas S. A., Cali, Colombia) as a test product and Rivotril® (Roche Químicos e Farmacêuticas S. A., Rio de Janeiro, Brazil) as a reference product, a bioavailability study was performed in 26 healthy volunteers. Test and reference products were administered under fasting conditions following a single dose, two-sequences, two treatments, crossover randomized design with a 28-day-washout period. Blood samples were obtained from 0 to 96 hours after dosing. Plasma clonazepam levels were determined by a validated high performance liquid chromatography with UV detection method (HPLC/UV). ABC0-96, ABC0-∞, Cmax, Tmax, t1/2, and ke, pharmacokinetic parameters were determined from plasma level-time profiles by a noncompartmental method. ln-trasformed ABC0-∞ and Cmax were tested for bioequivalence. 90%-confidence intervals for test/reference ratio of these parameters were 87.9% to 103.6% and 84.4% to 104.0%, respectively. These results were within the FDA acceptance range of 80% to 125% and it was concluded that both products were bioequivalent.

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