The most important factor in the maintenance of the integrity of epithelial barrier function is probably the delivery of nutrients in the gastrointestinal tract. The role of the different ingredients added should be clarified.
We studied the possible interaction between rifampin and doxycycline in 20 patients with brucellosis treated randomly with either doxycycline and streptomycin or doxycycline and rifampin. The doxycycline levels in the plasma of patients in the group treated with rifampin were significantly lower than those in the plasma of patients treated with doxycycline and streptomycin. Furthermore, clearance in patients treated with rifampin was significantly higher than that in patients treated with doxycycline and streptomycin, and consequently, the elimination half-life and the area under the concentration-time curve were significantly lower. There was no therapeutic failure or relapse in the group treated with doxycycline and streptomycin, whereas 2 of 10 patients in the group treated with doxycycline and rifampin had a therapeutic failure or relapse. The plasma doxycycline levels had an inverse correlation with plasma rifampin levels. In the group treated with rifampin, those who were rapid acetylators had lower levels of doxycycline. In conclusion, combined treatment with rifampin reduces the levels of doxycycline in plasma. These data suggest that therapeutic failures or relapses may result from this interaction.Brucellosis is still a serious public health problem in many parts of the world (43). Although the mortality rate as a result of this infection is low (12), it causes frequent complications, particularly those affecting the locomotor system, and these complications sometimes cause serious functional sequelae (3, 15).The organisms of the genus Brucella are known to have a high degree of "in vitro" susceptibility to a number of antimicrobial agents (11,36). However, their location, which is predominantly intracellular, protects them from the actions of many antibiotics. This explains to a great extent the tendency of this organism to cause illness with a long evolution and frequent relapses (41).For several decades the treatment of choice for brucellosis was based on the association of tetracyclines and streptomycin (13,29). Several studies carried out in the beginning of the 1980s showed that rifampin had excellent antibrucellar activity. This fact, together with its good intracellular penetration and ease of administration, made it a drug of great interest for the treatment of brucellosis (7,16,33).Studies with animal models and humans showed that rifampin monotherapy for brucellosis resulted in a high number of therapeutic failures and relapses (20,28). However, when it was used in combination with doxycycline there was a clear synergism and a good therapeutic efficacy (6).In 1986, the Expert Committee on Brucellosis of the Food and Agriculture Organization-World Health Organization recommended the combination of doxycycline-rifampin as the treatment of choice for human brucellosis (24). Later studies showed that the combination doxycycline-rifampin was less effective in practice than the classical treatment of tetracycline and streptomycin (1,14).
Developmental changes of repolarization are present in rabbits. These changes are in agreement with those reported in humans and may further support the role played by sex hormones in the modulation of cardiac repolarization.
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