Amprenavir（安普那韦） 药理作用： 　 是一种蛋白酶抑制剂。通过抑制病毒编码的蛋白酶，导致处理gag和gag-pol无能，产生无功能病毒。 　 适应证： 　 治疗HIV感染。 　 禁忌证： 　 禁用于对其任何成分在临床上过敏的患者。 　 药物剂型： 　 口服给药，胶囊，50mg、150mg，口服液，15mg/m1。 　 用法用量： 　 有50mg和150mg两种，常规每次1200mg，每天2次。可与或不与食物一起同服，但不能与脂类同服。 　 副作用： 恶心、腹泻、腹胀、皮疹。   Protease inhibitor Background U.S. Manufacturer GlaxoSmithKline Approval Amprenavir was approved by the U.S. Food and Drug Administration (FDA) in 1999 for use in adults and children with HIV infection. Approval was based on a study that found a higher rate of virologic suppression to undetectable levels after 24 weeks of treatment in subjects receiving amprenavir + zidovudine + lamivudine than in subjects receiving zidovudine + lamivudine.(1) There was no difference in CD4 T-lymphocyte counts between the two treatment arms. Subsequent follow-up showed viral load suppression to be sustained at 48 weeks. No studies of clinical end points have been reported. Formulation and Dosing Amprenavir has been available in capsules and oral solution. It is approved for twice-daily dosing; it also is approved for once-daily dosing in adults when used in combination with ritonavir. In October 2007, GlaxoSmithKline discontinued production and sale of amprenavir in the United States in order to focus on production of the amprenavir prodrug, fosamprenavir.(2) This action was not taken because of concerns about safety or efficacy of amprenavir. Amprenavir may continue to be available in some countries outside the United States. Fosamprenavir is available in the United States and elsewhere for adults and children 2 years of age and older. Dosing of Amprenavir Adult* Single PI 1,400 mg BID (oral solution)# Pediatric Neonate-4 years Not FDA approved; oral solution should not be used in children <4 years of age Age 4-12 years; or age 13-16 years and wt <50 kg 22.5 mg/kg BID or 17 mg/kg TID; maximum 2,800 mg/day (oral solution) 20 mg/kg BID or 15 mg/kg TID; maximum 2,400 mg/day (capsules) Age 13-16 years and wt ≥50 kg Adult dose Age >16 years Adult dose Key to abbreviations: PI, protease inhibitor; wt, weight; QD, once daily; BID, twice daily; TID, 3 times daily. * See fosamprenavir. # Not recommended unless other options are not available. Amprenavir should not be taken with a high-fat meal. Amprenavir, like its prodrug fosamprenavir, interacts with a number of antiretroviral medications; see Dosage Adjustments for ARV-ARV Drug Interactions for information on recommended dosing adjustments for fosamprenavir with other antiretrovirals. No dose adjustment is necessary in renal insufficiency. Please consult product labeling for detailed dosing information. FDA Pregnancy Category C. Clinical Use Combinations Rapid emergence of viral breakthrough occurs when amprenavir is used as monotherapy.(3) As with other antiretrovirals, amprenavir should be used only in combination regimens. Amprenavir is metabolized by the cytochrome P450 3A4 (CYP3A4) isoenzyme, and may alter the concentrations of other drugs metabolized by this pathway, including rifabutin, antiarrhythmics, tricyclic antidepressants, certain benzodiazepines, ergot derivatives, and others. Similarly, drugs that induce or inhibit the action of this isoenzyme may cause therapeutically significant alterations in amprenavir levels. For example, rifampin induces CYP3A4, and markedly decreases amprenavir levels. Information on drug interactions should be consulted, as dose adjustments are frequently required and some combinations are contraindicated. Although amprenavir has been studied in combination with all previously available protease inhibitors, in most cases precise information on dosing in combination with other antiretrovirals is lacking. Coadministration with lopinavir/ritonavir (Kaletra) may decrease amprenavir levels, and may require dose-adjustment of amprenavir.(4,5) Coadministration with efavirenz has been shown to decrease amprenavir levels, but increasing the amprenavir dose or adding ritonavir may boost amprenavir to therapeutic levels in combination with efavirenz.(6) Use in Initial vs Subsequent Therapy Treatment guidelines of the U.S. Department of Health and Human Services do not recommend amprenavir-containing regimens for initial treatment of HIV infection. The guidelines do include the amprenavir prodrug, fosamprenavir. Because amprenavir became available some time after the initial group of protease inhibitors, and because its associated resistance mutations differ from those of the other protease inhibitors, it has been studied as a possible component of salvage therapy in multiple-drug-experienced individuals. Efficacy in this situation appears to be modest. In protease inhibitor-experienced individuals, amprenavir plus a second protease inhibitor appears to be more effective than amprenavir alone in combination with NRTIs and efavirenz.(7) Factors Affecting Adherence Symptomatic side effects of amprenavir include rash, headache, diarrhea, and nausea. The amprenavir prodrug, fosamprenavir, has fewer gastrointestinal side effects. Amprenavir oral solution contains propylene glycol and should be avoided in certain patients, including pregnant women, young children, and those with renal or hepatic failure. It is important to assess patient motivation and discuss possible side effects and strategies for their management before treatment with amprenavir is initiated. Resistance Resistance to amprenavir is associated with the selection of 1 or more of several resistance mutations. Implications of amprenavir resistance for treatment with other antiretrovirals One resistance mutation (I50V) commonly selected by amprenavir does not appear to confer cross-resistance to other protease inhibitors, whereas others (I84V, M46I) confer or contribute to resistance against other protease inhibitors. In one study,(8) participants previously treated with amprenavir monotherapy showed long-term suppression of viral load after switching to a regimen of nevirapine + indinavir + stavudine + lamivudine. Genotypic or phenotypic testing may be useful in predicting the likelihood of response to other protease inhibitors following failure of regimens containing amprenavir. Implications of resistance to other antiretrovirals for amprenavir treatment A minority of individuals with HIV resistant to other protease inhibitors may respond to regimens including amprenavir. The addition of a second protease inhibitor appears to improve the rate of virologic response in highly drug-experienced patients.(7) Genotypic or phenotypic testing may be useful in predicting the likelihood of response to amprenavir following failure of regimens containing other antiretrovirals.