Fulco Patricia Pecora, Vora Urvi B, Bearman Gonzalo M L
Division of Infectious Diseases, Virginia Commonwealth University Medical Center, 401 N. 12th St., PO Box 980042, Richmond, VA 23298-0042, USA.
Ann Pharmacother. 2006 Nov;40(11):1974-83. doi: 10.1345/aph.1H022.
To review the literature associated with the pharmacokinetic interaction between protease inhibitors (PIs) and acid suppressive therapies and to characterize the impact of this interaction on virologic and immunologic outcomes.
A MEDLINE search (1966-October 2006) was conducted using the names of the 10 PIs and specific acid suppressive therapies including antacids, histamine(2)-receptor antagonists, and proton pump inhibitors. Abstracts and poster presentations from recent HIV/AIDS meetings were reviewed for relevance. References from retrieved articles, as well as product packaging and manufacturer information, were evaluated.
Pertinent pharmacokinetic, immunologic, and virologic studies, in healthy and HIV-infected patients, evaluating the use of a PI and acid suppressive therapy were reviewed.
Potential interactions between concomitant acid suppressive therapy and PIs were evaluated. Available information indicates that indinavir and atazanavir require an acidic gastric medium for adequate absorption. Indinavir pharmacokinetic parameters are variable with acid suppressive therapy but primarily result in decreased oral absorption. This interaction abates with concurrent ritonavir use. No immunologic or virologic data are available regarding the concomitant use of indinavir and acid suppressive therapy. The minimum concentration of atazanavir, area under the concentration-time curve, and maximum concentration are significantly reduced when used concurrently with acid suppressive therapy. Atazanavir 300 or 400 mg boosted with ritonavir 100 mg increases plasma concentrations when used with acid suppressive drugs. Virologic and immunologic outcomes appear stable when boosted atazanavir is used in HIV-positive patients. Atazanavir therapeutic monitoring should be considered when used in combination with acid suppressive therapy.
Of the PIs reviewed, significant pharmacokinetic interactions exist between acid suppressive therapy and indinavir or atazanavir. These PIs should be used with low-dose ritonavir if acid suppressive therapy is necessary.
回顾与蛋白酶抑制剂（PIs）和抑酸疗法之间药代动力学相互作用相关的文献，并描述这种相互作用对病毒学和免疫学结果的影响。
使用10种PIs的名称以及特定的抑酸疗法（包括抗酸剂、组胺-2受体拮抗剂和质子泵抑制剂）进行了MEDLINE检索（1966年 - 2006年10月）。对近期HIV/AIDS会议的摘要和海报展示进行了相关性审查。对检索到的文章的参考文献以及产品包装和制造商信息进行了评估。
对在健康和HIV感染患者中评估PIs与抑酸疗法联合使用的相关药代动力学、免疫学和病毒学研究进行了综述。
评估了同时使用抑酸疗法和PIs之间的潜在相互作用。现有信息表明，茚地那韦和阿扎那韦需要酸性胃介质以实现充分吸收。茚地那韦的药代动力学参数在使用抑酸疗法时会发生变化，但主要导致口服吸收减少。这种相互作用在同时使用利托那韦时会减弱。关于茚地那韦与抑酸疗法联合使用，尚无免疫学或病毒学数据。与抑酸疗法同时使用时，阿扎那韦的最低浓度、浓度 - 时间曲线下面积和最大浓度会显著降低。当与利托那韦100mg联用增强时，阿扎那韦300或400mg与抑酸药物合用时会增加血浆浓度。在HIV阳性患者中使用增强后的阿扎那韦时，病毒学和免疫学结果似乎稳定。当与抑酸疗法联合使用时，应考虑对阿扎那韦进行治疗监测。
在所审查的PIs中，抑酸疗法与茚地那韦或阿扎那韦之间存在显著的药代动力学相互作用。如果需要抑酸疗法，这些PIs应与低剂量利托那韦联合使用。
