PROBENECID AND ZIDOVUDINE METABOLISM
PROBENECID AND ZIDOVUDINE METABOLISM
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DOI：
10.1016/s0140-6736(89)92087-4
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发表时间：
1989-08
期刊：
影响因子：
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通讯作者：
D. Kornhauser;C. Hendrix;L. Nerhood;B. Petty;Amina Woods;J. Bartlett;P. Lietman
中科院分区：
文献类型：
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作者：
D. Kornhauser;C. Hendrix;L. Nerhood;B. Petty;Amina Woods;J. Bartlett;P. Lietman
在8名接受齐多夫定治疗人类免疫缺陷病毒感染的受试者中，研究了已知的葡萄糖醛酸化抑制剂probenecid对齐多夫定药代动力学的影响。在受试者单独服用齐多夫定时、齐多夫定加每8 h 500 mg丙苯昔3天后、齐多夫定加每8 h 500 mg丙苯昔加260 mg硫酸奎宁3天后测定齐多夫定血药浓度/时间曲线下面积中位数随丙苯昔的加入而增加80%。硫酸奎宁阻止了苯丙酸的作用，但在不服用苯丙酸的情况下对齐多夫定动力学没有影响。所有的影响都继发于齐多夫定代谢的改变，因为丙苯昔和奎宁都没有改变齐多夫定的肾脏消除。丙苯昔可与齐多夫定合用，延长给药间隔，减少齐多夫定日需药量，增加便捷性，降低成本。
The effects of probenecid, a known inhibitor of glucuronidation, on the pharmacokinetics of zidovudine were assessed in eight subjects receiving zidovudine as treatment for human immunodeficiency virus infection. Zidovudine plasma concentrations were measured while subjects were receiving zidovudine alone, after 3 days of zidovudine plus 500 mg probenecid every 8 h, and after 3 days of zidovudine plus 500 mg probenecid plus 260 mg quinine sulphate every 8 h. A median increase of 80% in the area under the zidovudine plasma concentration/time curve occurred with the addition of probenecid. Quinine sulphate prevented the probenecid effect but had no effect on zidovudine kinetics when taken without probenecid by four other subjects. All of the effects were secondary to changes in zidovudine metabolism, since neither probenecid nor quinine changed the renal elimination of zidovudine. Probenecid could be used in combination with zidovudine to extend the interval between doses and reduce the daily requirement for zidovudine, thus enhancing convenience and reducing costs.