Rifabutin

Các tên gọi khác (10 ) :

1,4-Dihydro-1-deoxy-1',4-didehydro-5'-(2-methylpropyl)-1-oxorifamycin xiv
4-Deoxo-3,4-(2-spiro(N-isobutyl-4-piperidyl)-2,5-dihydro-1H-imidazo)-rifamycin S
4-N-Isobutylspiropiperidylrifamycin S
Ansamicin
Ansamycin
Mycobutin (tn)
Rifabutin
Rifabutina
Rifabutine
Rifabutinum

Thuốc trị ký sinh trùng, chống nhiễm khuẩn

Thuốc Gốc

Small Molecule

CAS: 72559-06-9

ATC: J04AB04

ĐG : CQ International Co. Inc. , http://www.cqici.com

CTHH: C₄₆H₆₂N₄O₁₁

PTK: 847.0047

A broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients. [PubChem]

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₄₆H₆₂N₄O₁₁

Phân tử khối

847.0047

Monoisotopic mass

846.441508846

InChI

InChI=1S/C46H62N4O11/c1-22(2)21-50-18-16-46(17-19-50)48-34-31-32-39(54)28(8)42-33(31)43(56)45(10,61-42)59-20-15-30(58-11)25(5)41(60-29(9)51)27(7)38(53)26(6)37(52)23(3)13-12-14-24(4)44(57)47-36(40(32)55)35(34)49-46/h12-15,20,22-23,25-27,30,37-38,41,49,52-54H,16-19,21H2,1-11H3,(H,47,57)/b13-12+,20-15+,24-14-/t23-,25+,26+,27+,30-,37-,38+,41+,45-/m0/s1

InChI Key

InChIKey=ATEBXHFBFRCZMA-VXTBVIBXSA-N

IUPAC Name

(7S,11S,12R,13S,14R,15R,16R,17S,18S)-2,15,17-trihydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-1'-(2-methylpropyl)-6,23,32-trioxo-8,33-dioxa-24,27,29-triazaspiro[pentacyclo[23.6.1.1^{4,7}.0^{5,31}.0^{26,30}]tritriacontane-28,4'-piperidin]-1,3,5(31),9,19,21,25,29-octaen-13-yl acetate

Traditional IUPAC Name

SMILES

CO[C@H]1\C=C\O[C@@]2(C)OC3=C(C2=O)C2=C(C(O)=C3C)C(=O)C(NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)=C1NC3(CCN(CC3)CC(C)C)N=C21

Độ hòa tan

Minimally soluble (0.19 mg/mL)

logP

4.1

logS

-4.7

pKa (strongest acidic)

7.93

pKa (Strongest Basic)

8.62

PSA

205.55 Å²

Refractivity

232.64 m³·mol^-1

Polarizability

90.72 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

Dược Lực Học : Rifabutin is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (including Pseudomonas aeruginosa) and specifically Mycobacterium tuberculosis. Because of rapid emergence of resistant bacteria, use is restricted to treatment of mycobacterial infections and a few other indications. Rifabutin is well absorbed when taken orally and is distributed widely in body tissues and fluids, including the CSF. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine, but dose adjustments are unnecessary with renal insufficiency.

Cơ Chế Tác Dụng : A broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients. [PubChem] Rifabutin acts via the inhibition of DNA-dependent RNA polymerase in gram-positive and some gram-negative bacteria, leading to a suppression of RNA synthesis and cell death.

Dược Động Học :

▧ Absorption :
Rifabutin is readily absorbed from the gastrointestinal tract, with an absolute bioavailability averaging 20%.
▧ Protein binding :
85%
▧ Metabolism :
Hepatic. Of the five metabolites that have been identified, 25-O-desacetyl and 31-hydroxy are the most predominant. The former metabolite has an activity equal to the parent drug and contributes up to 10% to the total antimicrobial activity.
▧ Route of Elimination :
A mass-balance study in three healthy adult volunteers with 14C-labeled rifabutin showed that 53% of the oral dose was excreted in the urine, primarily as metabolites. About 30% of the dose is excreted in the feces.
▧ Half Life :
45 (± 17) hours
▧ Clearance :
* 0.69 +/- 0.32 L/hr/kg

Độc Tính : LD₅₀ = 4.8 g/kg (mouse, male)

Chỉ Định : For the prevention of disseminated Mycobacterium avium complex (MAC) disease in patients with advanced HIV infection.

Tương Tác Thuốc :

Abiraterone Strong CYP3A4 inducers may decrease levels of abiraterone. Monitor concomitant therapy closely.
Acenocoumarol Rifabutin may decrease the anticoagulant effect of acenocoumarol by increasing its metabolism.
Amitriptyline The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, amitriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if rifabutin is initiated, discontinued or dose changed.
Amoxapine The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, amoxapine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amoxapine if rifabutin is initiated, discontinued or dose changed.
Amprenavir Amprenavir may increase the effect and toxicity of rifabutin.
Anisindione Rifabutin, may decrease the anticoagulant effect of anisindione.
Atazanavir Atazanavir may increase levels/toxicity of rifabutin.
Atorvastatin Rifabutin may decrease the effect of atorvastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of atorvastatin if rifabutin is initiated, discontinued or dose changed.
Atovaquone Rifabutin decreases the effect of atovaquone
Bromazepam Rifabutin may decrease the serum concentration of bromazepam by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of bromazepam if rifabutin is initiated, discontinued or dose changed.
Bupropion Rifampin reduces bupropion levels
Buspirone Rifabutin decreases the effect of buspirone
Cabazitaxel Concomitant therapy with a strong CYP3A inducer may decrease concentrations of cabazitaxel. Avoid concomitant therapy.
Cerivastatin Rifabutin may decrease the effect of cerivastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of cerivastatin if rifabutin is initiated, discontinued or dose changed.
Clarithromycin The rifamycin, rifabutin, may decrease the effect of the macrolide, clarithromycin.
Clomipramine The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, clomipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if rifabutin is initiated, discontinued or dose changed.
Clozapine Rifabutin decreases the effect of clozapine
Cyclosporine The rifamycin decreases the effect of cyclosporine
Dapsone Decreased levels of dapsone
Delavirdine Rifabutin decreases the effect of delavirdine
Desipramine The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, desipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of desipramine if rifabutin is initiated, discontinued or dose changed.
Dicoumarol Rifabutin may decrease the anticoagulant effect of dicumarol.
Doxepin The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, doxepin, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if rifabutin is initiated, discontinued or dose changed.
Doxycycline The rifamycin decreases the effect of doxycycline
Erlotinib Decreased levels/effect of erlotinib
Erythromycin The rifamycin, rifabutin, may decrease the effect of the macrolide, erythromycin.
Estradiol valerate/Dienogest Affects CYP3A4 metabolism, decreases or effects levels of Estradiol valerate/Dienogest.
Ethinyl Estradiol Rifabutin may decrease the contraceptive effect of ethinyl estradiol. Hormonal contraception should not be solely relied on alone during concomitant therapy with rifabutin.
Etravirine Etravirine may experience a decrease in serum concentration. It is recommended to monitor etravirine therapy for efficacy. The combination of rifabutin and etravirine therapy is contraindicated if a protease inhibitor which is ritonavir boosted is also being used.
Fluconazole Fluconazole may increase levels/toxicity of rifabutin.
Fluvastatin Rifabutin may decrease the effect of fluvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of fluvastatin if rifabutin is initiated, discontinued or dose changed.
Fosamprenavir Amprenavir increases the effect and toxicity of rifabutin
Haloperidol The rifamycin decreases the effect of haloperidol
Imipramine The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, imipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if rifabutin is initiated, discontinued or dose changed.
Indinavir Rifabutin decreases the effect of indinavir
Itraconazole Rifabutin decreases the effect of itraconazole
Ivacaftor Strong CYP3A4 inducers may decrease levels of ivacaftor. Monitor concomitant therapy closely.
Josamycin The rifamycin, rifabutin, may decrease the effect of the macrolide, josamycin.
Lovastatin Rifabutin may decrease the effect of lovastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of lovastatin if rifabutin is initiated, discontinued or dose changed.
Mestranol This product may cause a slight decrease of the contraceptive effect
Methadone The rifamycin decreases the effect of methadone
Norethindrone Rifabutin may decrease the contraceptive effect of norethindrone. Hormonal contraception should not be solely relied on alone during concomitant therapy with rifabutin.
Nortriptyline The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, nortriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if rifabutin is initiated, discontinued or dose changed.
Pazopanib Affects CYP3A4 metabolism therefore will decrease levels or effect of pazopanib. Consider alternate therapy.
Posaconazole Modification of drug levels for both agents
Propafenone Rifampin decreases the effect of propafenone
Protriptyline The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, protriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of protriptyline if rifabutin is initiated, discontinued or dose changed.
Rilpivirine Strong inducers of CYP3A4 decrease the exposure of rilpivirine thus decreasing efficacy.
Ritonavir Rifabutin decreases the effect of ritonavir
Roflumilast Affects CYP3A4 metabolism, decreases level or effect of roflumilast.
Saquinavir Rifabutin decreases the effect of saquinavir
Simvastatin Rifabutin may decrease the effect of simvastatin by increasing its metabolism. Monitor for changes in the therapeutic effect of simvastatin if rifabutin is initiated, discontinued or dose changed.
Sirolimus The rifamycin decreases the effect of sirolimus
Sunitinib Possible decrease in sunitinib levels
Tacrolimus Carbamazepine may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Carbamazepine therapy is initiated, discontinued or altered.
Tamoxifen The rifamycin decreases the effect of anti-estrogen
Telithromycin Rifabutin may decrease the plasma concentration of Telithromycin. Consider alternate therapy.
Temsirolimus Rifabutin may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Terbinafine Rifabutin may increase the metabolism and clearance of Terbinafine. To avoid Terbinafine treatment failure, co-administration should be avoided.
Tipranavir Tipranavir increases the concentration of Rifabutin. Adjust Rifabutin dose and monitor for adverse/toxic effects.
Tolvaptan Rifabutin is a CYP3A4 inducer and will decrease serum concentrations of tolvaptan and ultimately, its clinical effects.
Toremifene The rifamycin decreases the effect of anti-estrogen
Tramadol Rifabutin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Trazodone The CYP3A4 inducer, Rifabutin, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Rifabutin is initiated, discontinued or dose changed.
Trimipramine The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, trimipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of trimipramine if rifabutin is initiated, discontinued or dose changed.
Vandetanib Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
Vemurafenib Strong CYP3A4 inducers may decrease levels of vemurafenib. Monitor concomitant therapy closely.
Verapamil Rifabutin, a CYP3A4 inducer, may decrease the serum concentration of Verapamil by increasing its metabolism (particularly in the intestinal mucosa) and decreasing its absorption. Monitor for changes in the therapeutic/adverse effects of Verapamil if Rifabutin is initiated, discontinued or dose changed.
Voriconazole Rifabutin may decrease the serum concentration of voriconazole likely by increasing its metabolism via CYP3A enzymes. Voriconazole may increase the serum concentration of rifabutin likely by inhibiting its metabolism via CYP3A. Concomitant therapy is contraindicated.
Warfarin Rifabutin may decrease the anticoagulant effect of warfarin by increasing its metabolism.
Zidovudine The rifamycin decreases levels of zidovudine

Liều Lượng & Cách Dùng : Capsule - Oral

Dữ Kiện Thương Mại

Giá thị trường

Biệt dược thương mại : Mycobutin 150 mg capsule

Giá bán buôn : USD >13.01

Đơn vị tính : capsule

Nhà Sản Xuất

Công ty : Pfizer

Sản phẩm biệt dược : Ansatipin
Công ty : SERB

Sản phẩm biệt dược : Ansatipine
Công ty : Pfizer

Sản phẩm biệt dược : Mycobutin
Công ty : Lupin

Sản phẩm biệt dược : Ributin

Đóng gói

Công ty : CQ International Co. Inc.

Website : http://www.cqici.com
Công ty : Kaiser Foundation Hospital
Công ty : Pfizer Inc.

Website : http://www.pfizer.com
Công ty : Pharmacia Inc.

Website : http://www.pharmaciaupjohn.com
Công ty : Physicians Total Care Inc.

Website : http://www.physicianstotalcare.com

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB00615

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=6323490

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506468

KEGG Compound

http://www.genome.jp/dbget-bin/www_bget?cpd:C07235

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D00424

ChemSpider

http://www.chemspider.com/Chemical-Structure.4883445.html

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0013-5301-17

PharmGKB

http://www.pharmgkb.org/drug/PA451249

Wikipedia

http://en.wikipedia.org/wiki/Rifabutin

RxList

http://www.rxlist.com/cgi/generic2/rifabutin.htm

Drugs.com

http://www.drugs.com/cdi/rifabutin.html

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