Posaconazole

Các tên gọi khác (1) :

SID144207169

antifungal agents

Thuốc Gốc

Small Molecule

CAS: 171228-49-2

ATC: J02AC04

ĐG : Patheon Inc. , http://www.patheon.com

CTHH: C₃₇H₄₂F₂N₈O₄

PTK: 700.7774

Posaconazole is a triazole antifungal drug that is used to treat invasive infections by Candida species and Aspergillus species in severely immunocompromised patients.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₃₇H₄₂F₂N₈O₄

Phân tử khối

700.7774

Monoisotopic mass

700.329708282

InChI

InChI=1S/C37H42F2N8O4/c1-3-35(26(2)48)47-36(49)46(25-42-47)31-7-5-29(6-8-31)43-14-16-44(17-15-43)30-9-11-32(12-10-30)50-20-27-19-37(51-21-27,22-45-24-40-23-41-45)33-13-4-28(38)18-34(33)39/h4-13,18,23-27,35,48H,3,14-17,19-22H2,1-2H3/t26-,27?,35-,37-/m0/s1

InChI Key

InChIKey=RAGOYPUPXAKGKH-AGDNISCASA-N

IUPAC Name

4-{4-[4-(4-{[(5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-1-[(2S,3S)-2-hydroxypentan-3-yl]-4,5-dihydro-1H-1,2,4-triazol-5-one

Traditional IUPAC Name

posaconazole

SMILES

CC[C@@H]([C@H](C)O)N1N=CN(C1=O)C1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(OCC2CO[C@](CN3C=NC=N3)(C2)C2=C(F)C=C(F)C=C2)C=C1

Độ hòa tan

Insoluble

logP

5.5

logS

-4.8

pKa (strongest acidic)

14.83

pKa (Strongest Basic)

3.93

PSA

111.79 Å²

Refractivity

200.71 m³·mol^-1

Polarizability

74.25 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

MDDR-Like Rule

true

Dược Lực Học : Posaconazole is an antifungal agent structurally related to itraconazole. It is a drug derived from itraconzaole through the replacement of the chlorine substituents with flourine in the phenyl ring, as well as hydroxylation of the triazolone side chain. These modifications enhance the potency and spectrum of activity of the drug. Posaconazole can be either fungicial or fungistatic in action.

Cơ Chế Tác Dụng : Posaconazole is a triazole antifungal drug that is used to treat invasive infections by Candida species and Aspergillus species in severely immunocompromised patients. As a triazole antifungal agent, posaconazole exerts its antifungal activity through blockage of the cytochrome P-450 dependent enzyme, sterol 14α-demethylase, in fungi by binding to the heme cofactor located on the enzyme. This leads to the inhibition of the synthesis of ergosterol, a key component of the fungal cell membrane, and accumulation of methylated sterol precursors. This results in inhibition of fungal cell growth and ultimately, cell death.

Dược Động Học :

▧ Absorption :
Posaconazole is absorbed with a median Tmax of approximately 3 to 5 hours.
▧ Volume of Distribution :
* 1774 L
▧ Protein binding :
Posaconazole is highly protein bound (>98%), predominantly to albumin.
▧ Metabolism :
Posaconazole primarily circulates as the parent compound in plasma. Of the circulating metabolites, the majority are glucuronide conjugates formed via UDP glucuronidation (phase 2 enzymes). Posaconazole does not have any major circulating oxidative (CYP450 mediated) metabolites. The excreted metabolites in urine and feces account for ~17% of the administered radiolabeled dose.
▧ Route of Elimination :
The excreted metabolites in urine and feces account for ~17% of the administered radiolabeled dose.
▧ Half Life :
Posaconazole is eliminated with a mean half-life (t½) of 35 hours (range 20 to 66 hours).
▧ Clearance :
* 32 L/hr * 51 L/hr [Single-Dose Suspension Administration of 200 mg, fasted] * 21 L/hr [Single-Dose Suspension Administration of 200 mg, nonfat meal] * 14 L/hr [Single-Dose Suspension Administration of 200 mg, high fat meal] * 91 L/hr [Single-Dose Suspension Administration of 400 mg, fasted] * 43 L/hr [Single-Dose Suspension Administration of 400 mg with liquid nutritional supplement (14 g fat)]

Độc Tính : During the clinical trials, some patients received posaconazole up to 1600 mg/day with no adverse events noted that were different from the lower doses. In addition, accidental overdose was noted in one patient who took 1200 mg BID for 3 days. No related adverse events were noted by the investigator.

Chỉ Định : For prophylaxis of invasive Aspergillus and Candida infections in patients, 13 years of age and older, who are at high risk of developing these infections due to being severely immunocompromised as a result of procedures such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD), or due to hematologic malignancies with prolonged neutropenia from chemotherapy. Also for the treatment of oropharyngeal candidiasis, including oropharyngeal candidiasis refractory to itraconazole and/or fluconazole. Posaconazole is used as an alternative treatment for invasive aspergillosis, Fusarium infections, and zygomycosis in patients who are intolerant of, or whose disease is refractory to, other antifungals.

Tương Tác Thuốc :

Apixaban Avoid combination. Otherwise, posaconazole will likely increase apixaban serum concentration.
Astemizole Contraindicated co-administration
Bromazepam Posaconazole may increase the serum concentration of bromazepam by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of bromazepam if posaconazole is initiated, discontinued or dose changed.
Cimetidine Significant decrease of posaconazole levels
Cisapride Contraindicated co-administration
Conivaptan Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Concomitant use of conivaptan with strong CYP3A4 inhibitors (e.g., azole antifungals) is contraindicated.
Cyclosporine Increased level of cyclosporine
Dantrolene Posaconazole 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 posaconazole is initiated, discontinued or dose changed.
Dihydroergotamine Contraindicated co-administration
Ergotamine Contraindicated co-administration
Fosphenytoin Modifications of drug levels for both agents
Halofantrine Contraindicated co-administration
Ivacaftor Strong CYP3A4 inhibitors may increase levels of ivacaftor. Monitor concomitant therapy closely.
Methysergide Contraindicated co-administration
Phenytoin Modifications of drug levels for both agents
Pimozide Contraindicated co-administration
Ponatinib Strong CYP3A4 inhibitors may increase levels of ponatinib. Monitor concomitant therapy closely.
Quinidine Contraindicated co-administration
Regorafenib Strong CYP3A4 inhibitors may increase levels of regorafenib.
Rifabutin Modification of drug levels for both agents
Rivaroxaban Use of rivaroxaban with agents that are strong inhibitors of both CYP3A4 and P-glycoproteins are contraindicated.
Tacrolimus The strong CYP3A4 inhibitor, Posaconazole, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Posaconazole is initiated, discontinued or dose changed.
Tadalafil Posaconzole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Tamoxifen Posaconazole may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
Tamsulosin Posaconazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Posaconazole is initiated, discontinued, or dose changed.
Telithromycin Posaconazole may increase the plasma concentration of Telithromycin. Consider alternate therapy or monitor therapeutic/adverse effects.
Temsirolimus Posaconazole may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Teniposide The strong CYP3A4 inhibitor, Posaconazole, 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 Posaconazole is initiated, discontinued or dose changed.
Terfenadine Contraindicated co-administration
Tiagabine The strong CYP3A4 inhibitor, Posaconazole, 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 Posaconazole is initiated, discontinued or dose changed.
Tipranavir Tipranavir may increase the serum concentration of Posaconazole. Posaconazole may increase the serum concentration of Tipranavir.
Tolterodine Posaconazole may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Tramadol Posaconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Trazodone The CYP3A4 inhibitor, Posaconazole, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Posaconazole is initiated, discontinued or dose changed.
Trimipramine The strong CYP3A4 inhibitor, Posaconazole, 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 Posaconazole is initiated, discontinued or dose changed.
Vardenafil Posaconazole, 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 Posaconazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Posaconazole is initiated, discontinued, or dose changed.
Verapamil Posaconazole, 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 Posaconazole is initiated, discontinued or dose changed.
Vinblastine Posaconazole, 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 Posaconazole is initiated, discontinued or dose changed.
Vincristine Posaconazole, 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 Posaconazole is initiated, discontinued or dose changed.
Vinorelbine Posaconazole, 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 Posaconazole is initiated, discontinued or dose changed.
Zolpidem Posaconazole, 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 posaconazole is initiated, discontinued or dose changed.
Zonisamide Posaconazole, 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 posaconazole is initiated, discontinued or dose changed.
Zopiclone Posaconazole, 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 posaconazole is initiated, discontinued or dose changed.

Liều Lượng & Cách Dùng : Suspension - Oral

Dữ Kiện Thương Mại

Giá thị trường

Biệt dược thương mại : Noxafil 40 mg/ml suspension

Giá bán buôn : USD >7.08

Đơn vị tính : ml

Nhà Sản Xuất

Công ty :

Sản phẩm biệt dược : Noxafil

Đóng gói

Công ty : Patheon Inc.

Website : http://www.patheon.com
Công ty : Schering Corp.

Website : http://www.schering.de
Công ty : Schering-Plough Inc.

Website : http://www.schering-plough.ca

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB01263

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=147912

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508639

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D02555

ChemSpider

http://www.chemspider.com/Chemical-Structure.130409.html

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0085-1328-01

PharmGKB

http://www.pharmgkb.org/drug/PA151958574

Wikipedia

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

RxList

http://www.rxlist.com/cgi/generic/noxafil.htm

Drugs.com

http://www.drugs.com/cdi/posaconazole-suspension.html

Bạn thấy hài lòng ?

Bạn chưa hài lòng ?

... loading