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药品详细

Nelfinavir(奈非那韦)

化学结构式图
中文名
奈非那韦
英文名
Nelfinavir
分子式
C32H45N3O4S
化学名
(3S,4aS,8aS)-N-tert-butyl-2-[(2R,3R)-2-hydroxy-3-[(3-hydroxy-2-methylphenyl)formamido]-4-(phenylsulfanyl)butyl]-decahydroisoquinoline-3-carboxamide
分子量
Average: 567.782
Monoisotopic: 567.313077633
CAS号
159989-64-7
ATC分类
J05A Direct acting antivirals
药物类型
small molecule
阶段
approved
商品名
Viracept (Hoffmann-La Roche);
同义名
1UN;AG1343;Nelfinavir mesylate;NFV;NLF;
基本介绍

A potent HIV-1 protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. [PubChem]

生产厂家
  • Agouron pharmaceuticals inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Kaldor SW, Kalish VJ, Davies JF 2nd, Shetty BV, Fritz JE, Appelt K, Burgess JA, Campanale KM, Chirgadze NY, Clawson DK, Dressman BA, Hatch SD, Khalil DA, Kosa MB, Lubbehusen PP, Muesing MA, Patick AK, Reich SH, Su KS, Tatlock JH: Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease. J Med Chem. 1997 Nov 21;40(24):3979-85. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • (Iso)quinolines and Derivatives
  • Benzamides
Substructures
  • Ethers
  • Hydroxy Compounds
  • Phenols and Derivatives
  • Amino Ketones
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Aliphatic and Aryl Amines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Benzoyl Derivatives
  • (Iso)quinolines and Derivatives
  • Alcohols and Polyols
  • Phenyl Esters
  • Benzamides
  • Piperidines
适应症
ANTIVIRALS 抗病毒;
药理
Indication Used in combination with other antiviral drugs in the treatment of HIV in both adults and children.
Pharmacodynamics Nelfinavir 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. Nelfinavir 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 Nelfinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
Absorption Well absorbed following oral administration.
Volume of distribution
  • 2 to 7 L/kg
Protein binding >98%
Metabolism
Primarily hepatic via cytochrome P450 (CYP450) enzymes. CYP3A and CYP2C19 appear to be the predominant enzymes that metabolize nelfinavir in humans. One major and several minor metabolites are found in plasma; the major oxidative metabolite has in vitro antiviral activity comparable to that of the parent drug.
Route of elimination The terminal half-life in plasma was typically 3.5 to 5 hours. The majority (87%) of an oral 750 mg dose containing 14C-nelfinavir was recovered in the feces; fecal radioactivity consisted of numerous oxidative metabolites (78%) and unchanged nelfinavir (22%). Only 1–2% of the dose was recovered in urine, of which unchanged nelfinavir was the major component.
Half life 3.5 - 5 hours
Clearance Not Available
Toxicity Oral LD50 is over 5g/kg in rats. Side effects include thirst and hunger, unexplained weight loss, increased urination, fatigue, and dry, itchy skin.
Affected organisms
  • Human Immunodeficiency Virus
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 349.84 °C Not Available
water solubility Slightly soluble Not Available
logP 6 Not Available
Predicted Properties
Property Value Source
water solubility 1.91e-03 g/l ALOGPS
logP 4.61 ALOGPS
logP 4.72 ChemAxon
logS -5.5 ALOGPS
pKa (strongest acidic) 9.32 ChemAxon
pKa (strongest basic) 8.18 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 4 ChemAxon
polar surface area 101.9 ChemAxon
rotatable bond count 10 ChemAxon
refractivity 162.67 ChemAxon
polarizability 63.8 ChemAxon
药物相互作用
Drug Interaction
Abacavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Nelfinavir. The antiviral response should be closely monitored.
Abiraterone Strong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
Acenocoumarol The protease inhibitor, nelfinavir, may increase the anticoagulant effect of acenocoumarol.
Alprazolam The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, alprazolam.
Amiodarone Nelfinavir may increase the effect and toxicity of amiodarone.
Anisindione The protease inhibitor, nelfinavir, may increase the anticoagulant effect of anisindione.
Aprepitant This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
Astemizole Increased risk of cardiotoxicity and arrhythmias
Atorvastatin Nelfinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if nelfinavir is initiated, discontinued or dose changed.
Bromazepam Nelfinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if nelfinavir is initiated, discontinued or dose changed. Dosage adjustments may be required.
Cabazitaxel Concomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
Chlordiazepoxide The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, chlordiazepoxide.
Ciclesonide Increased effects/toxicity of ciclesonide
Cisapride Increased risk of cardiotoxicity and arrhythmias
Clonazepam The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, clonazepam.
Clorazepate The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, clorazepate.
Cyclosporine The protease inhibitor, nelfinavir, may increase the effect of cyclosporine.
Dantrolene Nelfinavir may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if nelfinavir is initiated, discontinued or dose changed.
Darifenacin Nelfinavir, a strong CYP3A4 inhibitor, may decrease the metabolism of darifenacin/solifenacin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of darifenacin if nelfinavir is initiated, discontinued or dose changed.
Diazepam The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, diazepam.
Dicumarol The protease inhibitor, nelfinavir, may increase the anticoagulant effect of dicumarol.
Dihydroergotamine Nelfinavir increases the effect and toxicity of ergot derivative
Dihydroquinidine barbiturate Nelfinavir increases the effect and toxicity of quindine
Eletriptan The protease inhibitor, nelfinavir, may increase the effect and toxicity of eletriptan.
Eplerenone The protease inhibitor, nelfinavir, may increase the effect and toxicity of eplerenone.
Ergotamine Nelfinavir increases the effect and toxicity of ergot derivative
Erlotinib This CYP3A4 inhibitor increases levels/toxicity of erlotinib
Estazolam The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, estazolam.
Ethinyl Estradiol Ritonavir could decrease the contraceptive efficacy
Felodipine Nelfinavir increases the effect and toxicity of felodipine
Fentanyl The protease inhibitor, nelfinavir, may increase the effect and toxicity of fentanyl.
Flurazepam The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, flurazepam.
Fusidic Acid The protease inhibitor, nelfinavir, may increase the effect and toxicity of fusidic acid.
Halazepam The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, halazepam.
Lovastatin Nelfinavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
Mestranol Ritonavir could decrease the contraceptive efficacy
Methadone Nelfinavir decreases the effect of methadone
Midazolam The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, midazolam.
Nevirapine Nevirapine may decrease the effect of nelfinavir.
Pimozide Nelfinavir increases the effect and toxicity of pimozide
Ponatinib Strong CYP3A4 inhibitors may increase levels of ponatinib. Monitor concomitant therapy closely.
Prazepam The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, prazepam.
Quazepam The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, quazepam.
Quinidine Nelfinavir increases the effect and toxicity of quinidine
Quinidine barbiturate Nelfinavir increases the effect and toxicity of quinidine
Ranolazine Increased levels of ranolazine - risk of toxicity
Rifampin Rifampin decreases the effect of nelfinavir
Saxagliptin Nelfinavir is an inhibitor of CYP3A4 which increases exposure of saxagliptin. Decrease dose of saxagliptin to 2.5 mg per day.
Sildenafil The protease inhibitor, nelfinavir, may increase the effect and toxicity of sildenafil.
Simvastatin Nelfinavir may increase the effect and toxicity of simvastatin. Concomitant therapy should be avoided.
Solifenacin This potent CYP3A4 inhibitor slows darifenacin / solifenacin metabolism
St. John's Wort St. John's Wort decreases the effect of indinavir
Sunitinib Possible increase in sunitinib levels
Tacrolimus The protease inhibitor, Nelfinavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Nelfinavir therapy is initiated, discontinued or altered.
Tadalafil Nelfinavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Tamoxifen Nelfinavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
Tamsulosin Nelfinavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Nelfinavir is initiated, discontinued, or dose changed.
Telaprevir Telaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Telithromycin Nelfinavir may increase the plasma concentration of Telithromycin. Consider alternate therapy or monitor therapeutic/adverse effects.
Temsirolimus Nelfinavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Teniposide The strong CYP3A4 inhibitor, Nelfinavir, 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 Nelfinavir is initiated, discontinued or dose changed.
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Tiagabine The strong CYP3A4 inhibitor, Nelfinavir, 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 Nelfinavir is initiated, discontinued or dose changed.
Tolterodine Nelfinavir may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Topotecan The p-glycoprotein inhibitor, Nelfinavir, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Tramadol Nelfinavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Trazodone The protease inhibitor, Nelfinavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Nelfinavir is initiated, discontinued or dose changed.
Triazolam The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, triazolam.
Trimipramine The strong CYP3A4 inhibitor, Nelfinavir, 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 Nelfinavir is initiated, discontinued or dose changed.
Vardenafil Nelfinavir, 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.
Vemurafenib Strong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
Venlafaxine Nelfinavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Nelfinavir is initiated, discontinued, or dose changed.
Verapamil Nelfinavir, 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 Nelfinavir is initiated, discontinued or dose changed.
Vinblastine Nelfinavir, 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 Nelfinavir is initiated, discontinued or dose changed.
Vincristine Nelfinavir, 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 Nelfinavir is initiated, discontinued or dose changed.
Vinorelbine Nelfinavir, 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 Nelfinavir is initiated, discontinued or dose changed.
Voriconazole Nelfinavir may decrease the serum concentration of voriconazole likely by increasing its metabolism. Voriconazole may increase the serum concentration of nelfinavir by decreasing its metabolism. Consider alternate therapy or adjust doses and monitor for reduced voriconazole efficacy and increased nelfinavir adverse effects during concomitant therapy.
Warfarin The protease inhibitor, nelfinavir, may increase the anticoagulant effect of warfarin.
Zolpidem Nelfinavir, 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 nelfinavir is initiated, discontinued or dose changed.
Zonisamide Nelfinavir, 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 nelfinavir is initiated, discontinued or dose changed.
Zopiclone Nelfinavir, 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 nelfinavir is initiated, discontinued or dose changed.
食物相互作用
  • Food significantly increases absorption (2 to 3 times).
  • Take with food.

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