Vol.67 No.2 March 2019
Development of therapeutic drug monitoring for daptomycin
1)Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, Japan
2)Department of Clinical Infectious Diseases, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama
Abstract
Daptomycin is an antibiotic agent exhibiting antibacterial activity against a broad range of Gram-positive bacteria including those associated with multi-drug resistance. Therapeutic drug monitoring (TDM) of daptomycin is unnecessary and 4 mg/kg of daptomycin is administrated to patients with skin and soft tissue infections and 6 mg/kg of daptomycin is administrated to patients with sepsis and endocarditis. Good correlations between the antibacterial activity of daptomycin and the area under the curve (AUC)/minimum inhibitory concentration (MIC) have been reported in in vivo studies. However, no significant correlations have been shown between clinical benefit and the AUC/MIC in patients who are taking 4 mg/kg/day or 6 mg/kg/day of daptomycin. The elevation of creatine phosphokinase (CPK) and myopathy are major side effects of daptomycin and the risk of CPK elevation is increased in patients with minimum blood concentrations greater than 24.3 mg/L. On the other hand, the safety and tolerability of high-dose daptomycin have been reported in recent years. The concentrations of daptomycin are variable between patients and influenced by several factors such as renal function, hemodialysis, concentrations of albumin and body temperatures. Additionally, we should be careful in handling and storing daptomycin serum samples because the stability of daptomycin in serum is variable depending on the ambient temperature. To recommend initiating studies on TDM for daptomycin is difficult due to the lack of evidence establishing the correlation between the efficacy, or risk of side effects, and drug concentrations. We need to accumulate more data for the PKPD of daptomycin and continue to consider the necessity of TDM.
Key word
daptomycin, therapeutic drug monitoring, pharmacokinetics, pharmacodynamics
Received
June 11, 2018
Accepted
September 4, 2018
Jpn. J. Chemother. 67 (2): 149-154, 2019
