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In datacenters and cloud computing, Quality of Service (QoS) is an essential concept as access to shared resources, including solid state drives (SSDs), must be ensured. The previously proposed workload-aware budget compensation (WA-BC) scheduling algorithm is a device I/O scheduler for guaranteeing performance isolation among multiple virtual machines sharing an SSD. This paper aims to resolve the following three shortcomings of WA-BC: (1) it is applicable to only SR-IOV supporting SSDs, (2) it is unfit for various types of workloads, and (3) it manages flash memory blocks separately in an inappropriate manner. We propose the host-level WA-BC (hWA-BC) scheduler, which aims to achieve performance isolation between multiple processes sharing an open-channel SSD.

Jin Ah Jung,1 Soo-Yun Lee,2 Jung-Ryul Kim,1 Jae-Wook Ko,1,2 Seong Bok Jang,3 Su Youn Nam,3 Wooseong Huh1,41Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, 2Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, 3Yuhan Research Institute, Yuhan Corporation, 4Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaPurpose: Valsartan, an angiotensin-receptor blocker, and rosuvastatin, a competitive inhibitor of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, are frequently coadministered to treat patients with hypertension and dyslipidemia. The study reported here sought to evaluate the pharmacokinetic and pharmacodynamic interactions between rosuvastatin and valsartan in healthy Korean subjects. Subjects and methods: Thirty healthy male Korean subjects were administered with rosuvastatin (20 mg/day), valsartan (160 mg/day), and both drugs concomitantly for 4 days in a randomized, open-label, multiple-dose, three-treatment, three-period crossover study. Plasma concentrations of rosuvastatin, N-desmethyl rosuvastatin, and valsartan were determined using validated high-performance liquid chromatography with tandem mass spectrometry. Lipid profiles and vital signs (systolic and diastolic blood pressure and pulse rate) were measured for the pharmacodynamic assessment.Results: For rosuvastatin, the geometric mean ratios (90% confidence intervals [CIs]) of coadministration to mono-administration were 0.8809 (0.7873-0.9857) for maximum plasma concentration at steady state and 0.9151 (0.8632-0.9701) for area under the concentration–time curve (AUC) over a dosing interval at steady state. For valsartan, the geometric mean ratios (90% CIs) of those were 0.9300 (0.7946-1.0884) and 1.0072 (0.8893-1.1406), respectively. There were no significant differences in the metabolic ratio of N-desmethyl rosuvastatin AUC to rosuvastatin AUC between coadministration and rosuvastatin alone. No interaction was found in terms of systolic or diastolic blood pressure or lipid profiles. Combined treatment with valsartan and rosuvastatin was generally well tolerated without serious adverse events.Conclusion: The pharmacokinetic profiles of rosuvastatin and valsartan in combination were comparable with those of rosuvastatin and valsartan administered individually, suggesting that their individual pharmacokinetics were not affected by their coadministration. No dose adjustment was required and the results are supportive of a study in a larger patient population.Keywords: pharmacokinetics, pharmacodynamics, hypertension, dyslipidemia&nbsp

Jin Ah Jung,1 Soo-Yun Lee,2 Tae-Eun Kim,3 Jung-Ryul Kim,1 Chin Kim,4 Wooseong Huh,1,5 Jae-Wook Ko1,2 1Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, 2Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, 3Department of Clinical Pharmacology, Konkuk University Medical Center, 4Clinical Research Team, CKD Pharmaceuticals, 5Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Aims: Lobeglitazone has been developed for the treatment of type 2 diabetes mellitus. This study was conducted to evaluate potential drug–drug interactions between lobeglitazone and warfarin, an anticoagulant with a narrow therapeutic index.Methods: In this open-label, three-treatment, crossover study, 24 healthy male subjects were administered lobeglitazone (0.5mg) for 1–12days with warfarin (25mg) on day 5 in one period. After a washout interval, subjects were administered warfarin (25mg) alone in the other period. Pharmacokinetics of R- and S-warfarin and lobeglitazone, as well as pharmacodynamics of warfarin, as measured by international normalized ratio (INR) and factor VII activity, were assessed. Results: The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for area under the curve from time zero to the time of the last quantifiable concentration (AUClast) for warfarin + lobeglitazone: warfarin alone were 1.0076 (90% CI: 0.9771, 1.0391) for R-warfarin and 0.9880 (90% CI: 0.9537, 1.0235) for S-warfarin. The maximum observed plasma concentration (Cmax) values were 1.0167 (90% CI: 0.9507, 1.0872) for R-warfarin and 1.0028 (90% CI: 0.9518, 1.0992) for S-warfarin, both of which were contained in the interval 0.80–1.25. Lobeglitazone had no effect on the area under the effect–time curve from time 0 to 168hours (AUEC) of INR and factor VII activity, as demonstrated by the GMRs of 1.0091 (90% CI: 0.9872, 1.0314) and 0.9355 (90% CI: 0.9028, 0.9695), respectively. In addition, the pharmacokinetics of lobeglitazone was also unaffected by warfarin.Conclusion: Concomitant administration of lobeglitazone and warfarin was well tolerated. Lobeglitazone had no meaningful effect on the pharmacokinetics or pharmacodynamics of warfarin. These findings indicate that lobeglitazone and warfarin can be coadministered without dosage adjustments for either drug. Keywords: lobeglitazone, thiazolidinedione, warfarin, pharmacokinetics, pharma­codynamics

Background The aim of this study was to identify risk factors for invasive breast cancer in patients diagnosed with ductal carcinoma in situ (DCIS) on a preoperative biopsy. These factors were used to develop a nomogram for predicting the risk of invasion in the preoperative setting. Methods This was a retrospective analysis of patients who underwent surgical treatment for DCIS diagnosed before surgery between 1997 and 2009. Multivariable analysis was used to identify clinical, radiological and histopathological factors that may predict upstaging. A nomogram was developed to predict the probability of invasion using multiple logistic regression analysis. This nomogram was subsequently validated using another cohort of patients with a preoperative diagnosis of DCIS between 2010 and 2012. Results Upstaging to invasive cancer occurred in 123 (24.9 per cent) of 493 women treated between 1997 and 2009. A larger DCIS lesion (at least 15 mm), lack of hormone receptor expression, intermediate or high nuclear grade, diagnosis on core biopsy compared with vacuum-assisted biopsy, and non-cribriform subtype of DCIS were significantly associated with upstaging. A nomogram developed using these factors demonstrated good predictive performance (area under the receiver operating characteristic (ROC) curve (AUC) 0·823, 95 per cent confidence interval 0·787 to 0·860). The nomogram showed similar predictive performance in the validation data set, based on another 149 women (AUC 0·700, 0·613 to 0·786). Conclusion Upstaging to invasive cancer in women with a preoperative diagnosis of DCIS is common. A nomogram based on the five most significant factors related to upstaging accurately predicted invasive cancer. This nomogram may be useful when deciding whether to pursue axillary staging with sentinel lymph node biopsy in patients with DCIS.

Soo-Yun Lee,1 Wooseong Huh,2 Jin Ah Jung,3 Hye Min Yoo,2 Jae-Wook Ko,1,2 Jung-Ryul Kim2,4 1Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 2Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center,Seoul, 3Department of Clinical Pharmacology, Inje University, Busan Paik Hospital, Busan, 4Department of Clinical Research and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea Abstract: Valproic acid (VPA) is mainly metabolized via glucuronide, which is hydrolyzed by β-glucuronidase and undergoes enterohepatic circulation. Amoxicillin/clavulanic acid (AMC) administration leads to decreased levels of β-glucuronidase-producing bacteria, suggesting that these antibiotics could interrupt enterohepatic circulation and thereby alter the pharmacokinetics of VPA. This study aimed to evaluate the effects of AMC on the pharmacokinetics of VPA. This was an open-label, two-treatment, one-sequence study in 16 healthy volunteers. Two treatments were evaluated; treatment VPA, in which a single dose of VPA 500mg was administered, and treatment AMC + VPA, in which multiple doses of AMC 500/125mg were administered three times daily for 7days and then a single dose of VPA was administered. Blood samples were collected up to 48hours. Pharmacokinetic parameters were calculated using noncompartmental methods. Fifteen subjects completed the study. Systemic exposures and peak concentrations of VPA were slightly lower with treatment AMC + VPA than with treatment VPA (AUClast, 851.0h·mg/L vs 889.6h·mg/L; Cmax, 52.1mg/L vs 53.0mg/L). There were no significant between-treatment effects on pharmacokinetics (95% confidence interval [CI]) of AUClast and Cmax (95.7 [85.9–106.5] and 98.3 [91.6–105.6], respectively). Multiple doses of AMC had no significant effects on the pharmacokinetics of VPA; thus, no dose adjustment is necessary. Keywords: drug–drug interaction, pharmacokinetics, enterohepatic circulation

Aims: To compare the pharmacokinetics, pharmacodynamics, and safety of sarpogrelate between controlled-release (CR) and immediate-release (IR) formulations after multiple-dose administration. Methods: This study was a randomized, open-label, 2-period, 2-treatment, crossover study in healthy subjects. All subjects received CR sarpogrelate 300 mg once daily and IR sarpogrelate 100 mg three times daily by random order each for 3 days with a 7-day washout period. Serial blood sampling was performed over 24 h. Pharmacokinetic parameters were determined by noncompartmental methods. Platelet aggregation to collagen, measured by light transmission aggregometry, was reported as maximal platelet aggregation. Results: Thirty-two subjects completed the study. CR sarpogrelate increased rapidly, reaching Cmax in 1.25 h (vs. 1.00 h in IR sarpogrelate) and declined with a t1/2 of 3.59 h (vs. 1.12 h in IR sarpogrelate). The 90% CIs for the geometric mean ratio of AUCτ and Cmax,ss between IR and CR formulations were 1.18 to 1.40 and 0.99 to 1.29, respectively. The degree of inhibition of platelet aggregation was similar between two formulations. Conclusions: CR sarpogrelate showed slightly higher systemic exposure and similar peak concentration compared with IR sarpogrelate. The profiles of pharmacodynamics and safety were comparable between two formulations.

Background The Atopic Dermatitis Antecubital Severity (ADAS) score is a new objective scale for the assessment of the severity of atopic dermatitis (AD). It is calculated by multiplying the intensity of inflammatory signs by the size of an antecubital eczema lesion. Aim To test the validity, reliability, and sensitivity to changes of the ADAS score compared with those of the Eczema Area and Severity Index (EASI) score. Methods Forty patients with AD were enrolled and treated with a moisturizer. At baseline, and in weeks 1 and 2, two independent evaluators measured the ADAS score, the EASI score, and the investigator's global assessment score rated on a six-point scale. Results The ADAS score showed a higher validity than the EASI score. The superiority of the ADAS to the EASI was prominent in mild AD. Inter-evaluator reliability was excellent in both the ADAS score and the EASI. The sensitivity to changes was higher in the ADAS score than in the EASI score. Conclusions The ADAS score may be used as a simple scoring system with good validity, reliability, and sensitivity to changes, especially in patients with mild-to-moderate AD.

Soo-Yun Lee,1 Jung-Ryul Kim,2,3 Jin Ah Jung,4 Wooseong Huh,2,5 Mi Young Bahng,6 Jae-Wook Ko1,2 1Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea; 2Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Republic of Korea; 3Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea; 4Department of Clinical Pharmacology, Inje University, Busan Paik Hospital, Busan, Republic of Korea; 5Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 6Dong-A ST Co., Ltd., Seoul, Republicof Korea Abstract: A fixed-dose combination of amlodipine and olmesartan is used to treat high blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The objective of this study was to evaluate the bioequivalence of two fixed-dose combinations, ie, amlodipine orotate/olmesartan medoxomil 10/40 mg and amlodipine besylate/olmesartan medoxomil 10/40 mg, in healthy subjects. A randomized, open-label, single-dose, two-sequence, two-period, crossover study was conducted in 30 healthy adult volunteers. Blood samples were collected for up to 72 hours post-dose in each period. Safety data included the results of physical examinations, clinical laboratory tests, vital signs, an electrocardiogram, and adverse events. For both amlodipine and olmesartan, the 90% confidence intervals for the geometric mean ratios of AUClast and time to peak plasma concentration fell within the bioequivalence acceptance criteria. The two fixed-dose combinations showed similar safety profiles. Amlodipine orotate/olmesartan medoxomil 10/40 mg was bioequivalent to amlodipine besylate/olmesartan medoxomil 10/40 mg. Keywords: amlodipine orotate, amlodipine besylate, olmesartan medoxomil, fixed-dose combination, bioequivalence