Telavancin

Các tên gọi khác (2) :

TD-6424
Vibativ

Thuốc trị ký sinh trùng, chống nhiễm khuẩn

Thuốc Gốc

Small Molecule

CAS: 372151-71-8

ATC: J01XA03

CTHH: C₈₀H₁₀₇Cl₃N₁₁O₂₇P

PTK: 1792.096

Telavancin is a semi-synthetic derivative of vanocymycin that has bactericidal activity against Methicillin-resistant Staphylococcus aureus (MRSA is an important pathogen causing hospital-acquired pneumonia (HAP) worldwide) and other gram-positive bacteria. FDA approved on September 11, 2009.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₈₀H₁₀₇Cl₃N₁₁O₂₇P

Phân tử khối

1792.096

Monoisotopic mass

1789.614106906

InChI

InChI=1S/C80H106Cl2N11O27P.ClH/c1-7-8-9-10-11-12-13-14-21-85-22-23-87-80(5)32-57(115-37(4)71(80)103)119-70-68(102)67(101)55(34-94)118-79(70)120-69-53-28-41-29-54(69)117-52-20-17-40(27-46(52)82)65(99)63-77(109)91-61(78(110)111)43-30-50(96)44(33-86-35-121(112,113)114)66(100)58(43)42-25-38(15-18-49(42)95)59(74(106)93-63)90-75(107)60(41)89-73(105)48(31-56(83)97)88-76(108)62(92-72(104)47(84-6)24-36(2)3)64(98)39-16-19-51(116-53)45(81)26-39;/h15-20,25-30,36-37,47-48,55,57,59-65,67-68,70-71,79,84-87,94-96,98-103H,7-14,21-24,31-35H2,1-6H3,(H2,83,97)(H,88,108)(H,89,105)(H,90,107)(H,91,109)(H,92,104)(H,93,106)(H,110,111)(H2,112,113,114);1H/t37-,47+,48-,55+,57-,59+,60+,61-,62+,63-,64+,65+,67+,68-,70+,71+,79-,80-;/m0./s1

InChI Key

InChIKey=GSSIWSIRBWAZHG-ACOPVEIWSA-N

IUPAC Name

(1S,2R,18R,19R,22S,25R,28R,40S)-22-(carbamoylmethyl)-5,15-dichloro-48-{[(2S,3R,4S,5S,6R)-3-{[(2S,4S,5S,6S)-4-{[2-(decylamino)ethyl]amino}-5-hydroxy-4,6-dimethyloxan-2-yl]oxy}-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-2,18,32,35,37-pentahydroxy-19-[(2R)-4-methyl-2-(methylamino)pentanamido]-20,23,26,42,44-pentaoxo-36-{[(phosphonomethyl)amino]methyl}-7,13-dioxa-21,24,27,41,43-pentaazaoctacyclo[26.14.2.2³,⁶.2¹⁴,¹⁷.1⁸,¹².1²⁹,³³.0¹⁰,²⁵.0³⁴,³⁹]pentaconta-3,5,8(48),9,11,14,16,29(45),30,32,34(39),35,37,46,49-pentadecaene-40-carboxylic acid hydrochloride

Traditional IUPAC Name

SMILES

Cl.CCCCCCCCCCNCCN[C@@]1(C)C[C@H](O[C@@H]2[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]2OC2=C3OC4=CC=C(C=C4Cl)[C@@H](O)[C@@H](NC(=O)[C@@H](CC(C)C)NC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]4C(C=C2OC2=CC=C(C=C2Cl)[C@@H](O)[C@@H]2NC(=O)[C@H](NC4=O)C4=CC=C(O)C(=C4)C4=C(C=C(O)C(CNCP(O)(O)=O)=C4O)[C@H](NC2=O)C(O)=O)=C3)O[C@@H](C)[C@H]1O

Độ hòa tan

1.48e-02 g/l

logP

-6.2

logS

-5.1

pKa (strongest acidic)

1.55

pKa (Strongest Basic)

9.99

PSA

598.09 Å²

Refractivity

429.41 m³·mol^-1

Polarizability

175.05 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 : Telavancin is a semi-synthetic derivative of vancomycin, therefore the mode of bactericidal action is similar to vancomycin in which both antibiotics inhibit cell wall synthesis. Not only that, it displays concentration-dependent bactericidal action. Furthermore, telavancin is a more potent inhibitor (10-fold) of peptidoglycan synthesis and, unlike vancomycin, disrupts cell membrane integrity via its interaction with lipid II. AUC/MIC ratio best predicts the extent of in-vivo response in which the higher the ratio, the greater the bactericidal activity. The smallest ratio in which one would be able to observe no bacterial growth at 24 hours is 50. Maximal bactericidal activity is observed at a AUC/MIC ratio of 404.

Cơ Chế Tác Dụng : Telavancin is a semi-synthetic derivative of vanocymycin that has bactericidal activity against Methicillin-resistant Staphylococcus aureus (MRSA is an important pathogen causing hospital-acquired pneumonia (HAP) worldwide) and other gram-positive bacteria. FDA approved on September 11, 2009. Telavancin is a bactericidal lipoglycopeptide that is active against a broad range of gram-positive bacteria. Telavancin prevents polymerization of N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) and cross-linking of peptidoglycan by binding to D-Ala-D-Ala. As a result, inhibition of bacterial cell wall synthesis occurs. Furthermore, telavancin disrupts membrane potential and cell permeability as a result of the lipophillic side chain moiety. This additional bactericidal mechanism is what sets telavancin apart from vancomycin.

Dược Động Học :

▧ Absorption :
Telavancin demonstrates linear pharmacokinetics at doses between 1 and 12.5 mg/kg. Furthermore, 24 hours post-infusion of a dose of 7.5 to 15 mg/kg, activity against MRSA and penicillin-resistant Streptococcus pneumonia can still be observed. The trough concentration at this point of time is approximately 10 μg/mL. Telavancin also has poor bioavailability and must be administered over 30-120 minutes IV. Cmax, healthy subjects, 10 mg/kg = 93.6 ± 14.2 μg/mL; AUC (0- ∞), healthy subjects, 10 mg/kg = 747 ± 129 μg · h/mL; AUC (0-24h), healthy subjects, 10 mg/kg = 666± 107 μg · h/mL; Time to steady state = 3 days;
▧ Volume of Distribution :
Vss, healthy subjects, 10 mg/kg = 0.14 L/kg
▧ Protein binding :
>90% to serum albumin in a concentration independent manner (despite being highly protein bound, antimicrobial activity of telavancin is not affected)
▧ Metabolism :
Metabolism of telavancin does not involve the cytochrome P450 enzyme system. Primary metabolite is called THRX-651540, but the metabolite pathway has not been identified.
▧ Route of Elimination :
Urine with >80% as unchanged drug and <20% as hydroxylated metabolites (with dose of 10mg/kg); Feces (<1%)
▧ Half Life :
Terminal elimination half-life = 8 ± 1.5 hours (with normal renal function)
▧ Clearance :
Cl, healthy subjects, 10 mg/kg = 13.9 ± 2.9 mL/h/kg

Chỉ Định : Treatment of complicated skin infections caused by gram-positive bacteria like methicillin-susceptible or -resistant Staphylococcus aureus, vancomycin-susceptible Enterococcus faecalis, and Streptococcus pyogenes, Streptococcus agalactiae, or Streptococcus anginosus group.

Tương Tác Thuốc :

Amiodarone Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Arsenic trioxide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Astemizole Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Bepridil Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Cisapride Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Disopyramide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Ibutilide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Indapamide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Ondansetron Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Pentamidine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Pimozide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Procainamide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Quinidine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Saquinavir Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Sotalol Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Terfenadine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Liều Lượng & Cách Dùng : Injection, powder, for solution - Intravenous - 250 mg, 750 mg

Dữ Kiện Thương Mại

Nhà Sản Xuất

Công ty : Theravance Inc.

Sản phẩm biệt dược : Vibativ

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB06402

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D06057

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0469-3575-50

Wikipedia

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

RxList

http://www.rxlist.com/vibativ-drug.htm

Drugs.com

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

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