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药品详细

Ritonavir(利托那韦)

化学结构式图
中文名
利托那韦
英文名
Ritonavir
分子式
C37H48N6O5S2
化学名
1,3-thiazol-5-ylmethyl N-[(2S,3S,5S)-3-hydroxy-5-[(2S)-3-methyl-2-{[methyl({[2-(propan-2-yl)-1,3-thiazol-4-yl]methyl})carbamoyl]amino}butanamido]-1,6-diphenylhexan-2-yl]carbamate
分子量
Average: 720.944
Monoisotopic: 720.312760056
CAS号
155213-67-5
ATC分类
J05A Direct acting antivirals
药物类型
small molecule
阶段
approved
商品名
Norvir;Norvir Sec;
同义名
Abbott 84538;ritonavir;
基本介绍

An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. [PubChem]

生产厂家
  • Abbott laboratories
  • Abbott laboratories pharmaceutical products div
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
  • Phenethylamines
  • Polypeptides
  • Amphetamines
Substructures
  • Hydroxy Compounds
  • Carbamates and Derivatives
  • Amino Ketones
  • Ethers
  • Benzene and Derivatives
  • Ureas and Derivatives
  • Carboxylic Acids and Derivatives
  • Thiazoles
  • Phenethylamines
  • Polypeptides
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Imines
  • Alcohols and Polyols
  • Amphetamines
适应症
ANTIVIRALS 抗病毒;
药理
Indication Indicated in combination with other antiretroviral agents for the treatment of HIV-infection.
Pharmacodynamics Ritonavir 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. Ritonavir 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 Ritonavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
Absorption The absolute bioavailability of ritonavir has not been determined.
Volume of distribution Not Available
Protein binding 98-99%
Metabolism
Hepatic. Five metabolites have been identified. The isopropylthiazole oxidation metabolite (M-2) is the major metabolite and has antiviral activity similar to that of ritonavir, however, plasma concentrations are low. The cytochrome P450 enzymes CYP3A and CYP2D6 are primarily involved in the metabolism of ritonavir.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Ritonavir
N-Desmethylritonavir Details
Ritonavir
hydroxyritonavir Details
Route of elimination Not Available
Half life 3-5 hours
Clearance Not Available
Toxicity Human experience of acute overdose with ritonavir is limited. One patient in clinical trials took ritonavir 1500 mg/day for two days. The patient reported paresthesias which resolved after the dose was decreased. A post-marketing case of renal failure with eosinophilia has been reported with ritonavir overdose. The approximate lethal dose was found to be greater than 20 times the related human dose in rats and 10 times the related human dose in mice.
Affected organisms
  • Human Immunodeficiency Virus
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
water solubility Practically insoluble Not Available
logP 3.9 Not Available
Predicted Properties
Property Value Source
water solubility 1.26e-03 g/l ALOGPS
logP 4.24 ALOGPS
logP 5.22 ChemAxon
logS -5.8 ALOGPS
pKa (strongest acidic) 13.68 ChemAxon
pKa (strongest basic) 2.84 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 6 ChemAxon
hydrogen donor count 4 ChemAxon
polar surface area 145.78 ChemAxon
rotatable bond count 18 ChemAxon
refractivity 194.59 ChemAxon
polarizability 77.4 ChemAxon
药物相互作用
Drug Interaction
Abacavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Ritonavir. The antiviral response should be closely monitored.
Abiraterone Strong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
Alfuzosin Ritonavir increases the effect/toxicity of alfuzosin
Alprazolam The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, alprazolam.
Aminophylline Ritonavir decreases the effect of theophylline
Amiodarone Ritonavir increases the effect and toxicity of amiodarone
Amitriptyline Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if ritonavir if initiated, discontinued or dose changed.
Amoxapine Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, amoxapine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amoxapine if ritonavir if initiated, discontinued or dose changed.
Apixaban Avoid combination. Otherwise, ritonavir will likely increase apixaban serum concentration.
Aprepitant This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
Astemizole Increased risk of cardiotoxicity and arrhythmias
Atazanavir Association with dose adjustment
Atomoxetine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Atorvastatin Ritonavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if ritonavir is initiated, discontinued or dose changed.
Avanafil Co-administration with the strong CYP3A4 inhibitor ritonavir resulted in an approximate 13-fold increase in AUC0-inf and 2.4-fold increase in Cmax of avanafil.
Bepridil Ritonavir increases the effect and toxicity of bepridil
Bromazepam Ritonavir, 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 ritonavir is initiated, discontinued or dose changed. Dosage adjustments may be required.
Bupropion Ritonavir increases the effect and toxicity of bupropion
Buspirone Ritonavir increases the effect and toxicity of buspirone
Cabazitaxel Concomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
Canagliflozin Nonselective inducers of UGT enzymes may decrease levels of canagliflozin, thus decreasing efficacy. Consider increase the dose to 300 mg once daily.
Carbamazepine Ritonavir increases the effect of carbamazepine
Chlordiazepoxide The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, chlordiazepoxide.
Ciclesonide Increased effects/toxicity of ciclesonide
Cisapride Increased risk of cardiotoxicity and arrhythmias
Clomipramine Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if ritonavir if initiated, discontinued or dose changed.
Clonazepam The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, clonazepam.
Clorazepate The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, clorazepate.
Clozapine Ritonavir increases the effect and toxicity of clozapine
Cyclosporine The protease inhibitor, ritonavir, may increase the effect of cyclosporine.
Dantrolene Ritonavir 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 ritonavir is initiated, discontinued or dose changed.
Darifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Delavirdine Increases the effect of ritonavir
Desipramine Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, desipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of desipramine if ritonavir if initiated, discontinued or dose changed.
Diazepam The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, diazepam.
Digoxin Ritonavir increases levels/effect of digoxin
Dihydroergotamine The protease inhibitor, ritonavir, may increase the effect and toxicity of the ergot derivative, dihydroergotamine.
Diltiazem Ritonavir increases diltiazem levels
Doxepin Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if ritonavir if initiated, discontinued or dose changed.
Dronedarone Ritonavir is a strong CYP3A4 inhibitor in which concomitant use with dronedarone will significantly increase its exposure. Avoid concomitant use.
Eletriptan The protease inhibitor, ritonavir, may increase the effect and toxicity of eletriptan.
Eplerenone This protease inhibitor, ritonavir, may increase the effect and toxicity of eplerenone.
Ergotamine The protease inhibitor, ritonavir, may increase the effect and toxicity of the ergot derivative, ergotamine.
Erlotinib This CYP3A4 inhibitor increases levels/toxicity of erlotinib
Erythromycin Increased toxicity of both agents
Estazolam The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, estazolam.
Ethinyl Estradiol Ritonavir could decrease the contraceptive efficacy
Fentanyl Ritonavir increases the effect and toxicity of fentanyl/alfentanyl
Flecainide Ritonavir increases the toxicity of the anti-arrhythmic
Fluoxetine Increased risk of serotonin syndrome
Flurazepam The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, flurazepam.
Fluticasone furoate Strong CYP3A4 inhibitors may increase levels of fluticasone furoate. Consider alternative therapy.
Fusidic Acid The protease inhibitor, ritonavir, may increase the effect and toxicity of fusidic acid.
Gefitinib This CYP3A4 inhibitor increases levels/toxicity of gefitinib
Imipramine Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if ritonavir if initiated, discontinued or dose changed.
Indacaterol Strong inhibitors of CYP3A4 may increase levels of indacaterol. Monitor closely for adverse events.
Itraconazole Itraconazole may increase the effect and toxicity of ritonavir.
Ketoconazole Ketoconazole may increase the effect and toxicity of ritonavir.
Linagliptin CYP3A4 inhibitors may increase levels of linagliptin. Monitor concomitant therapy closely.
Lovastatin Ritonavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
Mefloquine Mefloquine decreases the effect of ritonavir
Meperidine Ritonavir increases the levels of analgesic
Methadone The protease inhibitor, ritonavir, may decrease the effect of methadone.
Midazolam The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, midazolam.
Nortriptyline Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if ritonavir if initiated, discontinued or dose changed.
Olanzapine Ritonavir decreases the effect of olanzapine
Oxtriphylline Ritonavir decreases the effect of theophylline
Pazopanib Ritonavir is a strong inhibitor of CYP3A4 thus increasing exposure of pazopanib.
Pimozide The protease inhibitor, ritonavir, may increase the effect and toxicity of pimozide.
Piroxicam Ritonavir increases the toxicity of piroxicam
Ponatinib Strong CYP3A4 inhibitors may increase levels of ponatinib. Monitor concomitant therapy closely.
Ponatinib Strong CYP3A4 inhibitors may increase levels of ponatinib. Monitor concomitant therapy closely.
Prasugrel Ritonavir is a inhibitor of CYP3A4, thus blocking the bioactivation of prasugrel. As a result, a reduction in prasugrel efficiency may be observed in patients.
Propafenone Ritonavir increases the effect and toxicity of propafenone
Propoxyphene Ritonavir increases the levels of analgesic
Quinidine Ritonavir increases the effect and toxicity of quinidine
Quinupristin This combination presents an increased risk of toxicity
Ranolazine Increased levels of ranolazine - risk of toxicity
Rifabutin Rifabutin decreases the effect of ritonavir
Rifampin Rifampin decreases the effect of ritonavir
Rivaroxaban Use of rivaroxaban with agents that are strong inhibitors of both CYP3A4 like ritonavir and P-glycoproteins are contraindicated.
Roflumilast Affects CYP1A2 metabolism; decreases level or effect of roflumilast.
Saxagliptin Ritonavir is an inhibitor of CYP3A4 which increases exposure of saxagliptin. Decrease dose of saxagliptin to 2.5 mg per day.
Silodosin Strong CYP3A4 inhibitors may increase levels of silodosin. Concomitant administration is contraindicated.
Tacrolimus The protease inhibitor, Ritonavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Ritonavir therapy is initiated, discontinued or altered.
Tadalafil Ritonavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Tamoxifen Ritonavir may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
Tamsulosin Ritonavir, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Ritonavir is initiated, discontinued, or dose changed.
Telaprevir Telaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Telithromycin Ritonavir may increase the plasma concentration of Telithromycin. Consider alternate therapy or monitor therapeutic/adverse effects.
Temsirolimus Ritonavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Teniposide The strong CYP3A4 inhibitor, Ritonavir, 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 Ritonavir is initiated, discontinued or dose changed.
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Theophylline Ritonavir decreases the effect of theophylline
Tiagabine The strong CYP3A4 inhibitor, Ritonavir, 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 Ritonavir is initiated, discontinued or dose changed.
Tolterodine Ritonavir may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Tolvaptan Ritonavir is a strong inhibitor of CYP3A4 and will increase serum concentrations of tolvaptan.
Topotecan The p-glycoprotein inhibitor, Ritonavir, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Tramadol Ritonavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Ritonavir may decrease the effect of Tramadol by decreasing active metabolite production.
Trazodone The protease inhibitor, Ritonavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Ritonavir is initiated, discontinued or dose changed.
Tretinoin The strong CYP2C8 inhibitor, Ritonavir, may decrease the metabolism and clearance of oral Tretinoin. Consider alternate therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Ritonavir is initiated, discontinued to dose changed.
Triazolam The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, triazolam.
Trimipramine The strong CYP3A4/CYP2D6 inhibitor, Ritonavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4/CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Ritonavir is initiated, discontinued or dose changed.
Vardenafil Ritonavir, a potent CYP3A4 inhibitor, may decrease the metabolism and clearance of Vardenafil. Concomitant therapy is contraindicated.
Vemurafenib Strong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
Venlafaxine Ritonavir, a CYP2D6 and CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 and CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Ritonavir is initiated, discontinued, or dose changed.
Verapamil Ritonavir, 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 Ritonavir is initiated, discontinued or dose changed.
Vinblastine Ritonavir, 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 Ritonavir is initiated, discontinued or dose changed.
Vincristine Ritonavir, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism and/or increasing efflux. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Ritonavir is initiated, discontinued or dose changed.
Vinorelbine Ritonavir, 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 Ritonavir is initiated, discontinued or dose changed.
Voriconazole Ritonavir may decrease the serum concentration of voriconazole by increasing its metabolism. Concomitant therapy with high dose ritonavir is contraindicated. Caution should be used with lower doses as decreased voriconazole efficacy may occur.
Zolpidem Ritonavir, 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 ritonavir is initiated, discontinued or dose changed.
Zonisamide Ritonavir, 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 ritonavir is initiated, discontinued or dose changed.
Zopiclone Ritonavir, 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 ritonavir is initiated, discontinued or dose changed.
Zuclopenthixol Ritonavir, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if ritonavir is initiated, discontinued or dose changed.
食物相互作用
  • Avoid St.John's Wort.
  • Take with food.

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