Background: The metabolism of drugs and other xenobiotics is mediated by enzymes whose activities can be modulated by different compounds. The activities of these modulators have the potential to be used to optimize d...
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Background: The metabolism of drugs and other xenobiotics is mediated by enzymes whose activities can be modulated by different compounds. The activities of these modulators have the potential to be used to optimize drug action, prevent toxicity, or identify the enzymes involved in a reaction. This approach requires that selective agents be used for specific enzymes. However, selectivity of action has been poorly characterized in vivo. Methods: This study investigated the effect of 3 and 28 days of treatment with quinidine (200 mg daily) and rifampin (INN, rifampicin) (600 mg daily) on the activities of four cytochrome P450 enzymes and N-acetyltransferase in 28 healthy young male volunteers divided into three groups with a cocktail of drug probes used, including caffeine, mephenytoin, debrisoquin (INN, debrisoquine), and dapsone. Results: Quinidine selectively and almost completely inhibited the activity of CYP2D6 from day 3 through day 28 without affecting any other enzymes. Rifampin showed evidence of time-dependent induction of the activities of all measured oxidative routes of metabolism but decreased the acetylation ratio in fast acetylators. The quinidine/rifampin combination resulted in selective CYP2D6 inhibition and induction of all other enzymes evaluated over this time period, suggesting that predictable complex interactions occur with the drug combination. Conclusions: These observations illustrate the value of simultaneous assessment of the effect of modulators on the activities of multiple specific enzymes with the drug cocktail approach.
Known antimalarial compounds from several chemical classes were tested for their ability to inhibit in vitro growth of microorganisms causing dental plaque and to prevent the development of plaque in a hamster model. ...
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Known antimalarial compounds from several chemical classes were tested for their ability to inhibit in vitro growth of microorganisms causing dental plaque and to prevent the development of plaque in a hamster model. Approximately a third of the compounds tested inhibited in vitro growth; however, none prevented development of plaque.
Sequential measurements of serum C-reactive protein (CRP), serum haptoglobin (Hp) and erythrocyte sedimentation rate (ESR) were made in 209 patients with rheumatoid arthritis (RA). Of them 78 were treated with gold, 7...
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Sequential measurements of serum C-reactive protein (CRP), serum haptoglobin (Hp) and erythrocyte sedimentation rate (ESR) were made in 209 patients with rheumatoid arthritis (RA). Of them 78 were treated with gold, 71 with dapsone and 60 with prednisone. The results were expressed as proportional changes in the measurements at 28 day intervals after treatment began. The period of study was 140 days. During treatment with gold and dapsone there were statistically significant gradual and progressive falls of similar magnitude in serum CRP and ESR. During treatment with prednisone serum CRP and ESR fell abruptly by 28 days and thereafter altered little. At 140 days prednisone had had the largest proportional effect on both measurements. During gold treatment the fall in serum Hp was similar to that of the ESR. Prednisone had little effect on Hp levels despite large falls in serum CRP and the ESR. Prednisone stimulates Hp synthesis or the divergence is an expression of the difference in type of effect between gold and prednisone on RA. The effect of dapsone on serum Hp was large and progressive. It partly reflects hemolysis and, since the hemolysis was not progressive, partly improvement in the RA. The results show the relative efficacy of the drugs and suggest that dapsone may be a useful alternative treatment for RA.
The mechanism of action of many antimycobacterial agents is poorly understood. To obtain preliminary information on whether the targets for some of these drugs might also occur in other bacteria, the in vitro activiti...
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The mechanism of action of many antimycobacterial agents is poorly understood. To obtain preliminary information on whether the targets for some of these drugs might also occur in other bacteria, the in vitro activities of selected agents against Escherichia coli, Bacillus subtilis and Staphylococcus aureus were determined. Dapsone, p-aminosalicylic acid and thiacetazone failed to inhibit the above organisms (MIC values > 100 μg/ml) that may therefore lack targets for these drugs. Capreomycin, viomycin and clofazimine demonstrated activity against some of the organisms (MIC values < 100 μg/ml) suggesting that the targets of these drugs may not be restricted to mycobacterial species. The agents were all potent inhibitors of Mycobacterium bovis bacille Calmette-Guerin (MIC values 0.08-0.5 μg/ml).
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