药品详细
Amprenavir(安普那韦)
化学结构式图
中文名
安普那韦
英文名
Amprenavir
分子式
C25H35N3O6S
化学名
(3S)-oxolan-3-yl N-[(2S,3R)-3-hydroxy-4-[N-(2-methylpropyl)(4-aminobenzene)sulfonamido]-1-phenylbutan-2-yl]carbamate
分子量
Average: 505.627
Monoisotopic: 505.224656557
Monoisotopic: 505.224656557
CAS号
161814-49-9
ATC分类
J05A Direct acting antivirals;J05A Direct acting antivirals
药物类型
small molecule
阶段
approved
商品名
Agenerase;Prozei;Vertex;
同义名
AMP;AMV;APV;VX-478;
基本介绍
Amprenavir is a protease inhibitor used to treat HIV infection.
生产厂家
- Glaxosmithkline
封装厂家
参考
| Synthesis Reference | Not Available |
| General Reference | Not Available |
剂型
规格
化合物类型
| Type | small molecule |
| Classes |
|
| Substructures |
|
适应症
ANTIVIRALS 抗病毒;
药理
| Indication | For the treatment of HIV-1 infection in combination with other antiretroviral agents. |
| Pharmacodynamics | Amprenavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Amprenavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. |
| Mechanism of action | Amprenavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles. |
| Absorption | Rapidly absorbed after oral administration in HIV-1-infected patients with a time to peak concentration (Tmax) typically between 1 and 2 hours after a single oral dose. The absolute oral bioavailability of amprenavir in humans has not been established. |
| Volume of distribution | Not Available |
| Protein binding | Very high (90%). Amprenavir has the highest affinity for alpha(1)-acid glycoprotein. |
| Metabolism |
Hepatic. Amprenavir is metabolized in the liver by the cytochrome P450 3A4 (CYP3A4) enzyme system. The 2 major metabolites result from oxidation of the tetrahydrofuran and aniline moieties. Glucuronide conjugates of oxidized metabolites have been identified as minor metabolites in urine and feces.
|
| Route of elimination | Not Available |
| Half life | 7.1-10.6 hours |
| Clearance | Not Available |
| Toxicity | Not Available |
| Affected organisms |
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| Pathways | Not Available |
理化性质
| Properties | |||||||||||||||||||||||||||||||||||||||||||
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| State | solid | ||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Predicted Properties |
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药物相互作用
| Drug | Interaction |
|---|---|
| Abacavir | The serum concentration of Abacavir may be decreased by protease inhibitors such as Amprenavir. The antiviral response should be closely monitored. |
| Acenocoumarol | Amprenavir may increase the anticoagulant effect of acenocoumarol by increasing its serum concentration. |
| Alprazolam | Amprenavir may increase the effect and toxicity of the benzodiazepine, alprazolam. |
| Aluminium | The antiacid decreases the absorption of amprenavir |
| Amiodarone | The protease inhibitor, amprenavir, may increase the effect and toxicity of amiodarone. |
| Anisindione | Amprenavir may increase the anticoagulant effect of anisindione by increasing its serum concentration. |
| Astemizole | Increased risk of cardiotoxicity and arrhythmias |
| Atorvastatin | Amprenavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Concomitant therapy is contraindicated. |
| Bepridil | Amprenavir may increase the effect and toxicity of bepridil. |
| Bismuth Subsalicylate | The antiacid decreases the absorption of amprenavir |
| Calcium | The antiacid decreases the absorption of amprenavir |
| Cisapride | Amprenavir may increase the effect and toxicity of cisapride. |
| Clorazepate | Amprenavir may increase the effect and toxicity of the benzodiazepine, clorazepate. |
| Cyclosporine | The protease inhibitor, amprenavir, may increase the effect of cyclosporine. |
| Delavirdine | Decreased levels of delavirdine with increased levels of amprenavir |
| Diazepam | Amprenavir may increase the effect and toxicity of the benzodiazepine, diazepam. |
| Dicumarol | Amprenavir may increase the anticoagulant effect of dicumarol by increasing its serum concentration. |
| Dihydroergotamine | Amprenavir may increase the serum concentration of dihydroergotamine. Concomitant therapy is contraindicated. |
| Dihydroxyaluminium | The antiacid decreases the absorption of amprenavir |
| Disulfiram | Increased irsk of side effects (oral solution) |
| Ergotamine | Amprenavir may increase the effect and toxicity of ergotamine. |
| Ethinyl Estradiol | Ritonavir could decrease the contraceptive efficacy |
| Fentanyl | The protease inhibitor, amprenavir, may increase the effect and toxicity of fentanyl. |
| Flurazepam | Amprenavir may increase the effect and toxicity of the benzodiazepine, flurazepam. |
| Fusidic Acid | The protease inhibitor, amprenavir, may increase the effect and toxicity of fusidic acid. |
| Lovastatin | Amprenavir may increase the serum concentration of the lovastatin. Concomitant therapy is contraindicated. |
| Magnesium | The antiacid decreases the absorption of amprenavir |
| Magnesium oxide | The antiacid decreases the absorption of amprenavir |
| Mestranol | Ritonavir could decrease the contraceptive efficacy |
| Methadone | The protease inhibitor, amprenavir, may decrease the effect of methadone. |
| Metronidazole | Increased risk of side effects (oral solution) |
| Midazolam | Amprenavir may increase the effect and toxicity of the benzodiazepine, midazolam. |
| Pimozide | Amprenavir may increase the effect and toxicity of pimozide. |
| Ranolazine | Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentratin of ranolazine by inhibiting its metabolism. Concomitant therapy is contraindicated. |
| Rifabutin | Amprenavir may increase the effect and toxicity of rifabutin. |
| Rifampin | In presence of rifampin anticipate decrease of amprenavir efficiency |
| Sildenafil | The protease inhibitor, amprenavir, may increase the effect and toxicity of sildenafil. |
| Simvastatin | Amprenavir may increase the effect and toxicity of simvastatin. Concomitant therapy is contraindicated. |
| St. John's Wort | St. John's Wort decreases the effect of indinavir |
| Tacrolimus | The protease inhibitor, Amprenavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Amprenavir therapy is initiated, discontinued or altered. |
| Tadalafil | Amprenavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity. |
| Tamoxifen | Amprenavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen. |
| Tamsulosin | Amprenavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Amprenavir is initiated, discontinued, or dose changed. |
| Telithromycin | Co-administration may result in altered plasma concentrations of Amprenavir and/or Telithromycin. Consider alternate therapy or monitor the therapeutic/adverse effects of both agents. |
| Temsirolimus | Amprenavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided. |
| Teniposide | The strong CYP3A4 inhibitor, Amprenavir, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Amprenavir is initiated, discontinued or dose changed. |
| Terfenadine | Increased risk of cardiotoxicity and arrhythmias |
| Tiagabine | The strong CYP3A4 inhibitor, Amprenavir, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Amprenavir is initiated, discontinued or dose changed. |
| Tolterodine | Amprenavir may decrease the metabolism and clearance of Tolterodine. Adjust the Tolterodine dose and monitor for efficacy and toxicity. |
| Tramadol | Amprenavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. |
| Trazodone | The protease inhibitor, Amprenavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Amprenavir is initiated, discontinued or dose changed. |
| Triazolam | Amprenavir may increase the effect and toxicity of the benzodiazepine, triazolam. |
| Trimipramine | The strong CYP3A4 inhibitor, Amprenavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Amprenavir is initiated, discontinued or dose changed. |
| Vardenafil | Amprenavir, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil. |
| Venlafaxine | Amprenavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Amprenavir is initiated, discontinued, or dose changed. |
| Verapamil | Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Amprenavir is initiated, discontinued or dose changed. |
| Vinblastine | Amprenavir, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Amprenavir is initiated, discontinued or dose changed. |
| Vincristine | Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Amprenavir is initiated, discontinued or dose changed. |
| Vinorelbine | Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Amprenavir is initiated, discontinued or dose changed. |
| Vitamin E | Increased serum levels of vitamin E |
| Voriconazole | Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of amprenavir by decreasing its metabolism. The serum concentration of voriconazole may be increased by amprenavir. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed. |
| Warfarin | Amprenavir may increase the anticoagulant effect of warfarin by increasing its serum concentration. |
| Zolpidem | Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zolpidem by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zolpidem if amprenavir is initiated, discontinued or dose changed. |
| Zonisamide | Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if amprenavir is initiated, discontinued or dose changed. |
| Zopiclone | Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if amprenavir is initiated, discontinued or dose changed. |
食物相互作用
- Avoid alcohol, especially with the oral solution since it contains propylene glycol which competes with alcohol for alcohol dehydrogenase metabolism.
- Take with or without food, however avoid lipid-rich meals.
- Vitamin E increases amprenavir bioavailability.
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