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This review was performed to investigate the effects on immune system, blood, tissues, and organs of treatment with aprepitant, a newly developed nonsteroidal anti-inflammatory drug, after intravenous administration in a randomized crossover study. The results are discussed using of 6 previous studies, two trials and one pilot study.
There is widespread generic actoplus met xr knowledge that anti-inflammatory drugs are effective at restoring the body's immune system to its proper functioning after an infection. However, the extent to which anti-inflammatory drugs exert this effect is controversial. The main challenge to application of anti-inflammatory drugs for this purpose is that inflammatory mediators such as interleukin, tumor necrosis factor, or the proinflammatory cytokines IL-6 and TNF-alpha may not be specifically eliminated from various organs by these drugs and other proinflammatory mediators may cause undesired effects ( 1 ).
The results were analyzed with use of one-way analysis variance with Newman–Keuls correction for small groups. Because of the different doses aprepitant used in the studies, there was a significant difference in the time courses of major parameters the immune system from both control of aprepitant and experimental groups as determined by paired T 2 -hyperintensities in some samples (P < 0.05). Post hoc analysis of variance showed that all the parameters significant differences as indicated (data not shown).
RESULTS
Treatment with APOP, a new anti-inflammatory drug
All experiments were performed at the Université Paris VII–Sorbonne on June 11, 2003. The following drugs were tested: aprepitant, 500,1000 mg every 12 hours for a total of 15 days, and metronidazole, 400 mg intravenously for a total of 4 days (the latter study was stopped because of no response).
Blood and peripheral tissue samples
In a cross-over, open-label study with 12 patients relapsing remitting MS, aprepitant was given in divided, four-dose, oral dosing schedule, administered in two 2-hour, 24-hour intervals. For each dose, a 5% blood sample was drawn. The first dose given at 0730 and the next 0930 h, last 15 minutes before the dose was repeated. two final treatments were given during the night. After dosing with aprepitant, the patients were observed for at least 5 days and blood samples were taken at weeks 6, 12, 18, 26, and 36 for the analysis of leukocyte counts and IL-6 concentrations (Fig. ). The same procedure was carried out after the same period of time with 500 mg every 2 hours for two 5-day oral doses (the latter study was stopped because of no response). The same pharmacokinetic study was carried out after the administration of 4 days with metronidazole. The pharmacokinetic parameters determined were determined.
Fig. View largeDownload slide Dose-response evaluation of immune parameters in the study with patients relapse-remitting MS and treated with the treatment aprepitant. Doses are indicated with numbers 1 to 8 and their time intervals are indicated from 0100 to 0930, 0330 1730, 1800 0300, and 0930 to h.
Fig. View largeDownload slide Dose-response evaluation of immune parameters in the study with patients relapse-remitting MS and treated with the treatment aprepitant. Doses are indicated with numbers 1 to 8 and their time intervals are indicated from 0100 to 0930, 0330 1730, 1800 0300, and 0930 to h.
In the study with 12 patients relapsing remitting MS and treated for one dose with aprepitant (500 mg every 12 hours), leukocyte and cell count were determined at the end of second and third dosing periods. The cells were stained with an antibody that recognizes the leukocyte cost of actoplus met activation marker CD68 ( Fig. ); IL-6 (2ng/ml) was also measured. The leukocyte count for each treatment period (week 6 to week 18) showed a significant actoplus met xr coupon reduction with aprepitant compared those observed after metronidazole treatment.
Tissue samples
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