[Pharmacological study and clinical effect of HIV protease inhibitor amprenavir]

Amprenavir is a novel protease inhibitor with antiviral activity, and was approved in the U.S. (AGEN-ERASE) in 1999 for use in combination with other antiretrovirals for the treatment of HIV infection. The drug is developed by Kissei Pharmaceuticals Co., Ltd. in Japan, approved in the same year, and has been distributed by them (PROZEI). Amprenavir achieves a viral load of less than 400 copies/ml when it is given in triple combination therapy in both therapy-naive patients and patients previously treated with nucleoside reverse transcriptase inhibitors (NRTI). The recommended dose of amprenavir is eight 150-mg capsules, twice daily, or 1200 mg, b.i.d. Amprenavir may be taken with or without a meal; however, it should not to be taken with high-fat meals because its oral bioavailability may possibly be affected by fat. One of the major concerns associated with anti-HIV agents is the resistance mutation development, and the presence of I50V, M46I/L, I47V, I54L/V and I84V genotype has been observed in amprenavir therapy experienced subjects. Differences in resistance patterns and resistance mutation interactions may have amprenavir recognized as an alternative choice of drugs in maintaining efficacy. Therefore, amprenavir is believed to add an important treatment option in HIV infection therapy. It should be noted that P450 isozyme CYP3A4 is responsible for amprenavir; thus, care must be taken to avoid combined amprenavir with drugs that affect the action of CYP3A4, that act on the production CYP3A4 substrates, or that are metabolized by CYP3A4 metabolism. Amprenavir is the fifth protease inhibitor approved in Japan, and it is important to understand its differential and identical properties from other protease inhibitors to maximize its efficacy.