[Short-course isoniazid and rifampin compared with isoniazid for latent tuberculosis infection: a randomized clinical trial]. / Pauta corta de isoniazida y rifampicina comparada con isoniazida para la infección latente de tuberculosis. Ensayo clínico aleatorizado.

INTRODUCTION: The aim of this study was to compare the adherence to, and side effects of a 3-month short-course treatment for latent tuberculosis infection as compared to the standard 6-month course. METHODS: Prospective, comparative, randomized, open trial including patients with a positive tuberculin skin test and appropriate criteria for treatment in accordance with the CDC guidelines, and excluding patients with HIV infection. Group I (6H) was assigned to isoniazid 300 mg per day for 6 months and Group II (3HR) was assigned to isoniazid 300 mg per day plus rifampin 600 mg per day for 3 months. The patients were followed up for five years. RESULTS: A total of 105 patients were included, among which 9 refused treatment; 45 patients were placed in Group I and 51 patients in Group II. Both groups were comparable at baseline. Hepatotoxicity was 44% in Group 6H and 29% in Group 3HR (P = 0.07). Hepatotoxicity was severe in 6.7% of Group 6H and 5.8% of Group 3HR, requiring treatment interruption in 4.4% and 1.9%, respectively (P = NS). Among the total, 75.6% of patients in group 6H, and 90.2% in group 3HR completed the study treatment (P = 0.05). Tuberculous disease was detected in only one patient in the 6H group, occurring in the second month of treatment. CONCLUSION: In the treatment of latent tuberculosis infection, a 3-month course of isoniazid plus rifampin resulted in better adherence and a lower percentage of discontinued treatments than a 6-month isoniazid course. Tolerance was similar in the two regimens.

Pauta corta de isoniazida y rifampicina comparada con isoniazida para la infección latente de tuberculosis. Ensayo clínico aleatorizado / Short-course isoniazid and rifampin compared with isoniazid for latent tuberculosis infection: A randomized clinical trial

Introducción. El objetivo principal del estudio fue comparar la adherencia y tolerancia de una pauta corta de 3 meses con una pauta estándar de 6 meses para el tratamiento de la infección tuberculosa latente. Métodos. Ensayo clínico prospectivo, comparativo, aleatorizado y abierto de pacientes con derivado proteico purificado (PPD) positivo y criterios de tratamiento según normas de los Centers for Disease Control and Prevention (CDC), excluyendo infección por virus de la inmunodeficiencia humana (VIH). La pauta I consistía en isoniazida (H) en dosis de 300 mg/día, 6 meses (6H) y la pauta II en isoniazida en dosis de 300 mg/día con rifampicina (R) 600 mg/día, 3 meses (3HR). Los pacientes fueron seguidos durante 5 años. Resultados. Se han incluido 105 pacientes, 9 rechazaron el tratamiento; 45 pacientes en la pauta I y 51 pacientes en la pauta II. Los 2 grupos eran comparables a nivel basal. La hepatotoxicidad (HTX) fue del 44% en el grupo 6H, y 29% en el grupo 3HR (p 5 0,07). La HTX fue grave en 6,7% en pauta 6H y 5,8% en pauta 3HR; que obligó a suspender el tratamiento en el 4,4 y el 1,9%, respectivamente (p 5 NS). La proporción de pacientes que completaron el tratamiento fue 75,6% del grupo 6H, frente a 90,2% del grupo 3HR (p 5 0,05). Sólo un paciente en el segundo mes de 6H presentó enfermedad tuberculosa. Conclusión. Una pauta corta de 3 meses con isoniazida y rifampicina favorece una mejor adherencia con menor número de abandonos que la pauta de isoniazida 6 meses en el tratamiento de la infección latente tuberculosa. La tolerancia de las 2 pautas es similar (AU)

Introduction. The aim of this study was to compare the adherence to, and side effects of a 3-month short-course treatment for latent tuberculosis infection as compared to the standard 6-month course. Methods. Prospective, comparative, randomized, open trial including patients with a positive tuberculin skin test and appropriate criteria for treatment in accordance with the CDC guidelines, and excluding patients with HIV infection. Group I (6H) was assigned to isoniazid 300 mg per day for 6 months and Group II (3HR) was assigned to isoniazid 300 mg per day plus rifampin 600 mg per day for 3 months. The patients were followed up for five years. Results. A total of 105 patients were included, among which 9 refused treatment; 45 patients were placed in Group I and 51 patients in Group II. Both groups were comparable at baseline. Hepatotoxicity was 44% in Group 6H and 29% in Group 3HR (P 5 0.07). Hepatotoxicity was severe in 6.7% of Group 6H and 5.8% of Group 3HR, requiring treatment interruption in 4.4% and 1.9%, respectively (P 5 NS). Among the total, 75.6% of patients in group 6H, and 90.2% in group 3HR completed the study treatment (P 5 0.05). Tuberculous disease was detected in only one patient in the 6H group, occurring in the second month of treatment. Conclusion. In the treatment of latent tuberculosis infection, a 3-month course of isoniazid plus rifampin resulted in better adherence and a lower percentage of discontinued treatments than a 6-month isoniazid course. Tolerance was similar in the two regimens (AU)

A medicinal-chemistry-guided approach to selective and druglike sigma 1 ligands.

Based on a medicinal-chemistry-guided approach, three novel series of druglike cycloalkyl-annelated pyrazoles were synthesized and display high affinity (pKi>8) for the sigma1 receptor. Structure-affinity relationships were established, and the different scaffolds were optimized with respect to sigma1 binding and selectivity versus the sigma2 receptor and the hERG channel, resulting in selective compounds that have Ki values (for sigma1) in the subnanomolar range. Selected compounds were screened for cytochrome P450 inhibition (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4), metabolic stability (rat and human liver microsomes), and cell-membrane permeability (Caco-2). They showed favorable in vitro ADME properties as well as favorable calculated druglike and experimental physicochemical properties. Furthermore, compounds 7 f and 17 a, for example, displayed high selectivity (affinity) for the sigma1 receptor against a wide range of other receptors (>60). With these valuable tool compounds in hand, we are further exploring the role of the sigma1 receptor in relevant animal models corresponding to such medicinal indications as drug abuse, pain, depression, anxiety, and psychosis.