vibativ_73964_73965.jpg機轉:

Telavancin hydrochloride is a lipoglycopeptide antibiotic, which has concentration-dependent bactericidal activity against Gram-positive bacteria. Telavancin works by binding to the bacterial membrane and disrupting membrane barrier function and by interfering with peptidoglycan polymerization and cross-linking, leading to an inhibition of cell wall synthesis (Prod Info VIBATIV IV injection, 2009).

相同機轉的藥物,還有Dalbavancin 和Oritavancin

你可以參考這兩篇文章:

Glycopeptide新一代抗生素

[Drugs]New Lipoglycopeptides A Comparative Review of Dalbavancin, Oritavancin and Telavancin

Vancomycin上市至今,已有半世紀的歷史。過去,它一直被視為對抗具有抗藥性革蘭氏陽性菌感染的最後一張王牌,但由於抗藥性金黃色葡萄球菌(methicillin-resistant Staphylococcus aureus; MRSA)的盛行,vancomycin成為疑似革蘭氏陽性菌感染的經驗療法首選藥物。在大量使用vancomycin的選擇性壓力下,1980年代,歐洲首先發現VRE,之後歐美地區,特別是加護病房的VRE比例,一直居高不下。而醫界所擔心的,更具致病性的金黃色葡萄球菌,不知何時會開始產生抗藥性,此惡夢也終於在二十世紀末成真。1997年日本報告了全世界第一個被vancomycin-intermediate S. aureus (VISA)感染的個案2002年美國更報告一例確定被vancomycin-resistant S. aureus (VRSA)感染的病例。

或許你會想到另外幾個藥物:Linezolid還有Synercid或是daptomycin,沒有想到沒關係,這邊有機轉圖給你參考一下:圖解藥理學~12抗生素機轉08

Telavancin是屬於lipoglycopeptide類的抗生素,它的殺菌作用可快速達到,對抗MRSA,VISA和VRSA的活性相當高,telavancin的藥物動力學也是屬於濃度-依賴型的模式,而作用機轉是多重性。Telavancin可以抑制transglycosylase的活性,導致細胞壁合成受阻,同時可以干擾細菌細胞膜,將改變細胞膜的電位,使得細胞滲透性受到改變,而造成細菌生存能力喪失。Telavancin在正常腎功能狀態,半衰期大約是7-9小時,而且此藥物有後抗生素效應長達4-6小時,目前研究顯示一天一次的給藥模式,可以達到最佳殺菌作用。Telavancin的phase II臨床試驗中,被用於治療複雜的皮膚和皮膚結構感染,以一天一次的治療方式與傳統標準對抗Staphylococcus spp.的penicillin類或vancomycin治療,互相比較其臨床效益及微生物根除率,結果顯示telavancin的臨床治療率是82%,比傳統標準模式69%高,而微生物根除率telavancin 84%,也比標準治療vancomycin模式74%高,而兩組發生不良反應的比例也相當。

而另外兩個:

Dalbavancin是屬於一種半合成且結構式與teicoplanin相似的glycopeptide類抗生素,可治療嚴重的革蘭氏陽性菌感染。在體外試驗中顯示,dalbavacin對抗S. aureus, coagulase-negative staphylococci, β-hemolytic
streptococci和viridan group streptococci比vancomycin或teicoplanin更有效益,但對Enterococcus菌株,特別是有Van A phenotype的E. faecium其MIC必須提高。在phase III的臨床試驗中,證實可以治療血行性感染和複雜的皮膚和皮膚結構感染。Dalbavacin的半衰期長達9-12天,所以可以一週投與一次即可
臨床試驗證實,dalbavacin起始劑量是1g,一週後再給予500mg,投與兩次劑量,即能治療大部分對dalbavacin敏感性菌株感染。Dalbavacin的作用機轉是利用干擾peptidoglycan 交聯(crosslinking),而達到抑制細菌細胞壁合成的功能

Oritavancin(LY333328)也是半合成glycopeptide類抗生素,它的結構式與vancomycin相似,但對抗Van A, Van B, Van C的抗藥性基因有所不同。Oritavancin對以上三種基因型的Enterococci的MIC分別是2.0, 1.5,
0.8μg/mL,而vancomycin則是 >1024, >256, >8μg/mL。Coyle等人的體外試驗顯示,oritavancin與vancomycin相比較下,oritavancin對抗於對penicillin類、macrolide類和ciprofloxin抗藥性的S. pneumoniae的殺菌活性,比vancomycin更快速。因此,oritavancin可能可以被用於多重抗藥性的S. pneumoniae感染的替代藥物
。在體外試驗顯示中顯示,oritavancin與gentamicin併用,對於大部分VSE, VRE,MRSA, GISA都有加成作用;oritavancin與ampicillin併用,對於三分之二的VRE有加成作用。在phase II臨床試驗,oritavancin與vancomy-cin相較之下,對於治療菌血症的S. aureus感染,不管是臨床治療或微生物根除的最終目標及效益,都證實oritavancin可有效控制S. aureus菌血症。Oritavancin在體外試驗顯示其藥物動力學為濃度-依賴型,且對MRSA的後抗生素效應有2.4-7.7小時,在VREF有1.9-4.3小時。Oritavancin最常出現的副作用是腹瀉、噁心、嘔吐、低血鉀及注射部位發生靜脈炎。

好的,繼續補上一些其他的資料:

結構式:

螢幕快照 2010-11-08 上午11.39.07.png

劑量:

Intravenous route

Infection of skin AND/OR subcutaneous tissue, Complicated

For the treatment of complicated skin and skin structure infections caused by susceptible Gram-positive bacteria, the recommended telavancin dosage is 10 milligrams/kilogram intravenously over 60 minutes every 24 hours for 7 to 14 days. The duration of telavancin therapy depends on the infection severity and patient response (Prod Info VIBATIV IV injection, 2009).

    Dosage in Renal Failure
The recommended dosage of telavancin is 7.5 milligram/kilogram (mg/kg) intravenously (IV) every 24 hours (hr) in patients with a creatinine clearance (CrCl) between 30 to 50 milliliters/minutes (mL/min) and 10 mg/kg IV every 48 hr in patients with a CrCl of 10 to 30 mL/min. The manufacturer does not provide dosage adjustment recommendations for patients with end-stage renal disease (CrCl less than 10 mL/min) or patients receiving hemodialysis (Prod Info VIBATIV IV injection, 2009).

    Dosage in Hepatic Insufficiency
Telavancin dosage adjustments are not necessary in patients with mild to moderate hepatic impairment (Prod Info VIBATIV IV injection, 2009).

Precaution:

1) pregnancy; risk of fetal harm; avoid use (Prod Info VIBATIV IV injection, 2009)
2) women of childbearing potential; serum pregnancy test prior to administration and effective method of contraception recommended (Prod Info VIBATIV IV injection, 2009)
3) concomitant use with drugs known to prolong the QT interval (Prod Info VIBATIV IV injection, 2009)
4) infusion reactions (eg, Red-man syndrome type reaction, urticaria, pruritus) have been reported; slowing or stopping the infusion may abate reaction (Prod Info VIBATIV IV injection, 2009)
5) nephrotoxicity (eg, increased serum creatinine, renal failure), new onset or worsening, has been reported; increased risk in patients with pre-existing kidney disease, diabetes mellitus, congestive heart failure, hypertension, or with concomitant use with drugs that affect renal function (eg, NSAIDs, ACE inhibitors, loop diuretics); monitoring recommended; dosage adjustment necessary in patients with a CrCl less than 50 mL/min (Prod Info VIBATIV IV injection, 2009)
6) QT prolongation has been reported; avoid use in patients with congenital long QT syndrome, known prolongation of QT interval, uncompensated heart failure, or severe left ventricular hypertrophy (Prod Info VIBATIV IV injection, 2009)
7) renal impairment, pre-existing; decreased efficacy has been reported in patients with moderate to severe baseline renal impairment (CrCl of 50 mL/min or less); risk of accumulation of solubilizer hydroxypropyl-beta-cyclodextrin (Prod Info VIBATIV IV injection, 2009)
8) report suspected adverse reactions to Astellas Pharma US, Inc at 1-800-727-7003 or the US Food and Drug Administration at 1-800-FDA-1088 or www.fda.gov/medwatch (Prod Info VIBATIV IV injection, 2009)

Teratogenicity/Effects in Pregnancy

U.S. Food and Drug Administration's Pregnancy Category: Category C

Crosses Placenta: Unknown

Clinical Management

There are no adequate and well-controlled studies of telavancin use during pregnancy. In animal studies, telavancin increased fetal malformations and decreased pup weight and survival at doses similar to recommended clinical doses. Therefore, telavancin use should be avoided during pregnancy unless the potential benefit to the mother outweighs the potential risk to the fetus. Women of childbearing potential are required to have a serum pregnancy test prior to telavancin administration. Additionally, women of childbearing potential should be advised to use effective contraception during telavancin use. A pregnancy registry has been established for pregnant patients who receive telavancin, and patients may be enrolled by calling 1-888-658-4228 (Prod Info VIBATIV IV injection, 2009).

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