Clinical pharmacokinetic and pharmacodynamic analysis of daptomycin and the necessity of high-dose regimen in Japanese adult patients. Issue 6 (June 2019)

• Record Type: Journal Article
• Authors: Urakami, Toshiharu; Hamada, Yohei; Oka, Yusuke; Okinaka, Tomohide; Yamakuchi, Hiroki; Magarifuchi, Hiroki; Aoki, Yosuke
• Is Part Of: Journal of infection and chemotherapy. Volume 25:Issue 6(2019:Jun.)
• Page Start: 437
• Page End: 443
• Publication Date: 2019-06
• Subjects: Daptomycin -- Pharmacokinetic -- Pharmacodynamic -- Japanese -- Dose optimization; Chemotherapy -- Periodicals; Infection -- Periodicals; Communicable diseases -- Chemotherapy -- Periodicals; 615.5805
• DOI: 10.1016/j.jiac.2019.01.011
• Languages: English
• ISSNs: 1341-321X

Abstract

Abstract: The objective of this study was to explore the optimal dosage regimen of daptomycin and to determine the necessity and validity of a high-dose regimen from the perspectives of PK/PD parameters using Monte Carlo Simulation (MCS) and therapeutic drug monitoring (TDM) in a Japanese clinical setting. The volume of distribution (0.13 ± 0.012 L/kg) in this study was greater than that in healthy volunteers reported in Japan. The range of half-lives was between 8.9 and 34.9 h, which were gradually prolonged as creatinine clearance decreased. In MCS, the cumulative fractions of response (CFR) of the peak/MIC ≧ 60 and the AUC/MIC ≧ 666 at the 6 mg/kg q 24 h were 72.0% and 78.8% but at the 10 mg/kg q 24 h, the CFRs improved to both 99%. In TDM with 6 mg/kg q 24 h regimen, the patients who reached the peak and AUC target were 40% (2 out of 5 patients), respectively. The intraindividual variability in daptomycin PK may indicate the necessity of TDM and high-dose regimen, such as over 8 mg/kg, may be needed to ensure the effectiveness especially on Japanese patients with normal renal function.