Dalbavancin: pharmacokinetic and pharmacodynamic parameters
Azanza JR (1), Sádaba B (2), Reis J (3).
(1) Servicio de Farmacología Clínica, Clínica Universidad de Navarra, Pamplona, España.
(2) Servicio de Farmacología Clínica, Clínica Universidad de Navarra, Pamplona, España.
(3) Servicio de Farmacología Clínica y Unidad de Ensayos Clínicos, Clínica Universidad de Navarra, Pamplona, España.
Magazine: Enfermedades Infecciosas y Microbiología Clínica
Date: Jan 15, 2017Clinical Pharmacology [SP]
Dalbavancin is a new lipoglycopeptide antibiotic whose structure influences its pharmacokinetic profile. It is not absorbed after oral administration and is therefore administered intravenously.
It is distributed through intracellular fluid, reaching adequate concentrations in the skin, bone, blister fluid and synovial fluid. Plasma protein binding is very high.
Concentrations in brain tissue and cerebrospinal fluid (CSF) are inadequate. Excretion is through non-microsomal metabolism with inactive metabolites and through the kidneys by glomerular filtration.
Dalbavancin is eliminated slowly, as shown by its clearance value and its terminal elimination half-life, which exceeds 300 hours. This means that adequate concentrations of the drug remain in plasma and tissues for a prolonged period and explains the dosing regimen: a first dose of 1g followed 7 days later by a 500mg dose.
The pharmacokinetics are linear and show little intra- and interindividual variability. There are no pharmacokinetic interactions. Dose adjustment is not required for patients with mild or moderate renal insufficiency (creatinine clearance ≥ 30 to 79ml/min).
Dosage adjustment is not required in patients regularly receiving elective haemodialysis (3 times/week) and the drug can be administered without consideration of haemodialysis times.
In patients with chronic renal insufficiency, whose creatinine clearance is < 30ml/min and who are not regularly receiving elective haemodialysis, the recommended dose should be reduced to 750mg per week, followed 1 week later by 375mg. Dosage adjustment does not seem necessary in patients with liver failure or in older patients.
There is no information on the most appropriate dosage in children. The pharmacokinetic/pharmacodynamics parameter that best describes the effectiveness of dalbavancin is the ratio between the area under the curve and the minimum inhibitory concentration.
CITATION Enferm Infecc Microbiol Clin. 2017 Jan;35 Suppl 1:22-27. doi: 10.1016/S0213-005X(17)30031-9.
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