The influence of probiotic treatment on sulfasalazine metabolism in rat

被引:41
作者
Lee, Hee Ji [1 ]
Zhang, Hu [1 ]
Orlovich, David A. [2 ]
Fawcett, J. Paul [1 ]
机构
[1] Univ Otago, Sch Pharm, Dunedin 9054, New Zealand
[2] Univ Otago, Dept Bot, Dunedin 9054, New Zealand
关键词
Sulfasalazine; probiotics; metabolism; pharmacokinetics; rat; INFLAMMATORY-BOWEL-DISEASE; EPITHELIAL BARRIER FUNCTION; 5-AMINOSALICYLIC ACID; RHEUMATOID-ARTHRITIS; CLINICAL PHARMACOKINETICS; ENZYME-ACTIVITIES; FECAL MICROFLORA; GUT MICROFLORA; BACTERIA; SALICYLAZOSULFAPYRIDINE;
D O I
10.3109/00498254.2012.660508
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
1. Probiotics are live microorganisms claimed to exert beneficial effects on the host. This study investigated their effect on the metabolism and pharmacokinetics of sulfasalazine (SSZ), a drug whose efficacy depends on metabolism by azoreductase (AR) in the gut microbiota to sulfapyridine (SP) and 5-acetylsalicylic acid (5-ASA). 2. The probiotic strains Lactobacillus acidophilus L10, Bifidobacterium lactis B94 and Streptococcus salivarius K12 possessed AR activity and a corresponding ability to metabolize SSZ. 3. Treatment of male Wistar rats (n = 5) with oral 2 g doses of a mixture of the three probiotics (total dose 1.8 x 10(9) cfu) every 12 h for 3 days resulted in a significant increase (p < 0.05) in AR activity in ex vivo colon contents with a corresponding increase in SSZ metabolism. 4. Similar probiotic treatment of male Wistar rats (n = 8) followed by an oral 100 mg/kg dose of SSZ produced high plasma levels of SP, but pharmacokinetic parameters of SSZ and SP were not significantly different from control rats given SSZ. 5. These results indicate that probiotic strains possess AR activity and can metabolize SSZ. Treatment with probiotics increases AR activity in the gut microbiota but has no effect on plasma levels of SSZ and SP following a subsequent oral dose of SSZ.
引用
收藏
页码:791 / 797
页数:7
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