If Cpeak is ≧15 μg/mL, Cpeak/MIC achieves 8 or higher even in strains with an MIC of 2 μg/mL. Considering maximal concentrations that a drug achieves immediately after the completion of drug administration (Cmax) are higher than concentrations after completion of distribution (Cpeak), Cpeak must be lower than 15 μg/mL in aforementioned studies using Cmax. Three clinical studies targeting a higher Cpeak have recently been reported. Firstly, Kimura et al. [16] performed a clinical study GSK2118436 setting the target Cpeak of ABK at 15–20 μg/mL in patients with pneumonia and sepsis caused by MRSA.
The mean Cpeak was 17.2 μg/mL, and the rate of patients with a trough value of <2 μg/mL was 87.2% (34/39). A favorable response was achieved in 35 of 43 patients (81.4%). Secondly, Yamamoto et al. [17] performed a prospective clinical study, setting the target Cpeak and trough value at 20 and <2 μg/mL, in patients with pneumonia and bacteremia caused by MRSA. The mean Cpeak was 22.7 ± 5.5 μg/mL, a clinical and bacteriological effect was obtained in 66.7% (6/9), and 62.5% (5/8), respectively. Lastly, Matsumoto et al. set initial target Cpeak at 15–20 μg/mL and evaluated clinical efficacy and safety of ABK in patients with MRSA sepsis and pneumonia. The mean Cpeak was 16.2 μg/mL, and the efficacy rate was 89.7% [19]. a. Once daily administration is recommended from efficacy and safety viewpoints (B-II). The ideal and corrected body weights
are calculated using the CHIR-99021 mouse equations below: Idealbodyweight:Idealbodyweight(kg)=Height(m)×height(m)×22 Corrected body weight [20]: Underweight(actualbodyweight/idealbodyweight<1):Actualbodyweight×1.13 Overweight(morbidobesity)(actualbodyweight/idealbodyweight>2):0.43(actualbodyweight−idealbodyweight)+idealbodyweight The clinical response rates in patients who were administered 150–200 mg once daily were 89.5% in bacteremia and 80.8% in pneumonia, and these tended to be higher than those in patients with twice daily administration of same total daily dose of ABK (66.7% in bacteremia and 66.7%, in pneumonia) [10] and [21]. In an efficacy evaluation
of 200 mg once daily administration of ABK in patients with MRSA pneumonia, clinical and bacteriological effects were obtained in 74.4% and 46.2%, respectively [12]. In another study in 111 patients with pneumonia caused by MRSA treated with 200 mg/day of ABK, click here the clinical response rate was significantly higher in once daily administration group compared with twice daily group (69.6% vs. 50.8%) [9]. As mentioned above, target Cpeak 15–20 μg/mL was not achieved with once daily administration of the approved dose of 150–200 mg, and higher dosing regimen is required to improve clinical efficacy. In three clinical studies targeting a higher Cpeak, Kimura et al. [16] prepared nomogram based on parameters of population pharmacokinetics in consideration of the body weight, renal function, and age. With 5.