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An initial dosing method for teicoplanin based on the area under the serum concentration time curve required for MRSA eradication
Authors:Naoko Kanazawa  Kazuaki Matsumoto  Kazuro Ikawa  Tomohide Fukamizu  Akari Shigemi  Keiko Yaji  Yoshihiro Shimodozono  Norifumi Morikawa  Yasuo Takeda and Katsushi Yamada
Institution:(1) Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan;(2) Department of Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan;
Abstract:Teicoplanin is a glycopeptide antibacterial agent that has a long serum half-life and therefore takes time to achieve steady-state conditions. An appropriate initial dosing is needed for teicoplanin to promptly reach an effective serum trough concentration. However, little information is available on tailoring the initial dosing for patients with various characteristics. The objective of this study was to develop a nomogram for determining teicoplanin initial dose to promptly reach an effective trough concentration (≥13 μg/mL). A logistic regression analysis was performed to test whether the area under the concentration time curve (AUC) is a significant predictor of microbiological response (persistence 0; eradication 1). The study included 24 adult patients with methicillin-resistant Staphylococcus aureus infections minimal inhibitory concentration (MIC) for the isolates was <2 μg/mL). Each AUC was estimated using individual dose, creatinine clearance (CLcr), and body weight data. The target value, which gives about a 0.9 microbiological eradication probability, was 750 μg h/mL for AUC from zero to 24 h (AUC0–24 h). Using published population pharmacokinetic parameters, the dose required to achieve the AUC0–24 h target was calculated as dose (mg) = 750 × (0.00498 × CLcr (mL/min) + 0.00426 × body weight (kg). For various combinations of CLcr and body weight, we checked the calculated doses using a therapeutic drug monitoring (TDM)-supporting software and developed a nomogram. The nomogram would be useful for initial dose adjustment to promptly reach an effective serum trough concentration and avoid adverse events of teicoplanin.
Keywords:Teicoplanin  Nomogram  Loading dose  AUC
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