Daptomycin 메커니즘, PK/PD 특성

 

Daptomycin_wikipedia

 

 

Daptomycin

• cyclin lipopeptide계 항생제
• froom organism Streptomyces roseosporus
• MRSA, VRE를 포함한 Gram (+) bacteria

 

	INDICATION
Label	Bloodstream infection Endocarditis Skin and skin structure infection(eg, erysipelas, cellulitis, necrotizing infections)
Off label	Cerebrospinal fluid shunt infection Diabetic foot infection(moderate to severe) Intracranial abscess or spinal epidural abscess Meningitis Osteomyelitis Prosthetic joint infection Septic arthritis
Limitation	pulmonary infection(Pulmonary surfactant inactivates daptomycin) <1세 이하 유아(due to likely effects on the muscular, neuromuscular, and/or nervous systems)

 

MECHANISM OF ACTION

세균의 세포막 기능을 교란시켜 파괴함 → 막 전위의 빠른 탈분극화(repid depolarization of membrane potential)

⇒ only active against gram-positive bacteria

 

PHARMACODYNAMIC/PHARMACOKINETIC

Inhibition of bacterial growth	Bactericidal
PK/PD parameter	AUC:MIC
The onset of action	rapid onset of action
Distribution	건강한 성인 : 약 1.0 L/kg (at steady state) 소아/중증 환자 : significantly lower(각각 0.11 ± 0.02 L/kg vs 0.23 ± 0.14 L/kg) 그 외 장기 - Bone(cancellous) fCmax (plasma)/fCmax (tissue) ratio, steady state: 75% fAUCtissue/fAUCplasma ratio, steady state: 117%  bone/plasma ratio, single dose, ~7 hours postdose: ~8% to 10%  - CSF CSF:plasma ratio: AUC24 0.45%; Cmax 0.24% - Synovial fluid single dose, ~7 hours postdose:plasma ratio ~54%
Protein Binding	90% to 93% CrCl < 30 mL/min : 84% to 88%
Metabolism	Minor amounts of oxidative metabolites have been detected
Clearance	신기능 정상 & 성인 환자 : 8.3 to 9 mL/min/kg 소아 : 성인보다 큼
Half-life	신기능 정상 & 성인 환자 : 8 to 9 hours 신부전 환자 : up to 28 hr
Excretion	unchanged drug in the urine (78%) with a lesser amount eliminated in feces (5.7%)

 

 

reference:

1) wikipedia

2) lexicomp

3) www.ncbi.nlm.nih.gov/books/NBK470407/