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Dongjin Shin,1,* Juhyun Kim,1,* Jang Ho Lee,2,* Jong-Il Kim,1,3– 5 Yeon-Mok Oh2 1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; 2Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 3Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Republic of Korea; 4Genomic Medicine Institute, Seoul National University, Seoul, Republic of Korea; 5Seoul National University Cancer Research Institute, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Jong-Il Kim, Department of Biomedical Sciences, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea, Tel +82-2-740-8246, Email jongil@snu.ac.kr Yeon-Mok Oh, Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea, Tel +82-2-3010-3136, Fax +82-2-3010-6968, Email ymoh55@amc.seoul.krPurpose: The aim of the study was to use RNA sequencing (RNA-seq) data of lung from chronic obstructive pulmonary disease (COPD) patients to identify the bacteria that are most commonly detected. Additionally, the study sought to investigate the differences in these infections between normal lung tissues and those affected by COPD.Patients and Methods: We re-analyzed RNA-seq data of lung from 99 COPD patients and 93 non-COPD smokers to determine the extent to which the metagenomes differed between the two groups and to assess the reliability of the metagenomes. We used unmapped reads in the RNA-seq data that were not aligned to the human reference genome to identify more common infections in COPD patients.Results: We identified 18 bacteria that exhibited significant differences between the COPD and non-COPD smoker groups. Among these, Yersinia enterocolitica was found to be more than 30% more abundant in COPD. Additionally, we observed difference in detection rate based on smoking history. To ensure the accuracy of our findings and distinguish them from false positives, we double-check the metagenomic profile using Basic Local Alignment Search Tool (BLAST). We were able to identify and remove specific species that might have been misclassified as other species in Kraken2 but were actually Staphylococcus aureus, as identified by BLAST analysis.Conclusion: This study highlighted the method of using unmapped reads, which were not typically used in sequencing data, to identify microorganisms present in patients with lung diseases such as COPD. This method expanded our understanding of the microbial landscape in COPD and provided insights into the potential role of microorganisms in disease development and progression.Keywords: chronic obstructive pulmonary disease, next-generation sequencing, microbiome, metagenomics

Hyungmi An,1 Dongseong Shin2,3 1Institute of Convergence Medicine, Ewha Womans University Mokdong Hospital, Seoul, Korea; 2Department of Pharmacology, Gachon University College of Medicine, Incheon, Korea; 3Clinical Trials Center, Gachon University Gil Medical Center, Incheon, KoreaCorrespondence: Dongseong ShinDepartment of Pharmacology, Gachon University College of Medicine, 21, Namdong-daero 774 Beon-gil, Namdong-gu, Incheon, 21565, KoreaTel +82-32-460-9459Fax +82-32-460-9443Email dsshin@gilhospital.comBackground and Objective: Bioequivalence tests are fundamental step in assessing the equivalence in bioavailability between a test and reference product. In practice, two separate linear mixed models (LMMs) with random subject effects, which have an area under the concentration-time curve (AUC) and the peak concentration (Cmax) as the responses, have become the gold standard for evaluating bioequivalence. Recently, Lee et al developed a multivariate hierarchical generalized linear model (HGLM) for several responses that modeled correlations among multivariate responses via correlated random effects. The objective of this study was to apply this multivariate analysis to the bioequivalence test in practice and to compare the performance of multivariate HGLM and separate LMMs.Methods: Three pharmacokinetic datasets, fixed-dose combination (naproxen and esomeprazole), tramadol and fimasartan data were analyzed. We compared the 90% confidence interval (CI) for the geometric mean ratio (GMR) of a test product to a reference product using the multivariate HGLM and two conventional separate LMMs.Results: We found that the 90% CIs for the GMRs of both AUC and Cmax from the multivariate HGLM were narrower than those from the separate LMMs: (0.843, 1.152) vs (0.825, 1.177) for Cmax of esomeprazole in fixed-dose combination data; (0.805, 0.931) vs (0.797, 0.941) for Cmax in tramadol data; (0.801, 1.501) vs (0.762, 1.578) for Cmax and (1.163, 1.332) vs (1.009, 1.341) for AUC in fimasartan data, consistent with the random subject effects from two separate LMMs being highly correlated in the three datasets (correlation coefficient r = 0.883; r = 0.966; r = 0.832).Conclusion: This multivariate HGLM had good performance in the bioequivalence test with multiple endpoints. This method would provide a more reasonable option to reduce the 90% CI by adding correlation parameters and thus an advantage especially in evaluating the bioequivalence of highly variable drugs with broad 90% CIs.Keywords: bioequivalence test, correlated multiple responses, multivariate random effects model, H-likelihood, multivariate HGLM

Zirconium based amorphous alloys are suitable for biomedical applications because of their excellent corrosion resistance and biocompatibility. In this study, Zr48Cu36Al9Ag7 amorphous alloy was fabricated by arc melting and ingot converted into the plate-shaped amorphous alloy by the suction method in a water cooled copper mold. Scalpels of the amorphous alloy were fabricated by using the polishing method. The X-ray diffraction and differential scanning calorimetry confirmed the amorphous nature of the Zr48Cu36Al9Ag7 alloy. Elemental confirmation of the amorphous alloy was confirmed with X-ray photoelectron spectroscopy analysis. The hardness of amorphous alloy was compared with a commercial stainless steel scalpel. The observed corrosion potentials of the stainless steel scalpel and Zr48Cu36Al9Ag7 amorphous scalpel were − 0.6 V and − 0.4 V, respectively which confirms that the corrosion resistance of the amorphous alloy is better than stainless steel. The biomedical application of the Zr48Cu36Al9Ag7 amorphous alloy scalpel is supported by a comparative study that examined in vitro cytotoxicity, cell viability, and wound healing tests and compared it with the standard stainless steel scalpel. [ABSTRACT FROM AUTHOR]

Donghoon Shin,1 Younsoo Kim,1 Ahra Go,1 Maria Velinova2 1Samsung Bioepis Co., Ltd., Incheon, Republic of Korea; 2PRA International, Groningen, the NetherlandsCorrespondence: Donghoon ShinSamsung Bioepis Co., Ltd, 107, Cheomdan-daero, Yeonsu-gu, Incheon 21987, Republic of KoreaTel +82-31-8061-4534Fax +82-31-8061-4393Email dh01.shin@samsung.comPurpose: SB4 is an etanercept biosimilar, approved by the European Commission (EC) and the US Food and Drug Administration (FDA) following a demonstration of equivalent efficacy and safety and comparable quality data to the reference product. This study aimed to demonstrate equivalent pharmacokinetic (PK) profiles, safety, and tolerability between SB4 autoinjector (AI) and SB4 pre-filled syringe (PFS).Patients and methods: This was an open-label, two-period, two-sequence, single-dose, cross-over study to evaluate bioequivalence of PK profiles, safety, and tolerability between SB4 AI and PFS in healthy adults. Treatment periods were separated by 14 days resulting in a 35-day washout between investigational product (IP) administration in Periods 1 and 2.Results: A total of 50 subjects were randomized: 24 subjects in Sequence I and 26 in Sequence II, and 6 subjects discontinued from the study. The primary PK endpoints including area under the concentration–time curve from time zero to infinity (AUCinf) and to the last quantifiable concentration (AUClast), and maximum serum concentration (Cmax) were all within the equivalence margin of 80.00–125.00%. Safety and tolerability were comparable between the two treatments.Conclusion: PK profiles showed that SB4 AI and PFS were bioequivalent in healthy subjects. Safety assessment was also comparable between the two treatments.Keywords: biosimilar, etanercept, bioequivalence, autoinjector, pre-filled syringe

Dongseong Shin,1–3 Sang-In Park,4,5 Hong-Sub Lee,6 Kyung-Mi An,6 Juyoung Jung,6 MyongJae Lee,6 Kyung-Sang Yu31Department of Pharmacology, Gachon University College of Medicine, Incheon, Korea; 2Clinical Trials Center, Gachon University Gil Medical Center, Incheon, Korea; 3Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea; 4Department of Clinical Pharmacology and Therapeutics, Kyung Hee University Hospital, Seoul, Korea; 5East-West Medical Research Institute, Kyung Hee University, Seoul, Korea; 6Research Laboratories ILDONG Pharmaceutical Co. Ltd, Hwaseong, KoreaBackground and objective: IDP-73152 mesylate is a peptide deformylase inhibitor under investigation for the treatment of complicated skin and respiratory tract infections. The objective of this study was to investigate the pharmacokinetic (PK) profile and tolerability of IDP-73152 and the effect of food after a single oral administration.Methods: A dose block-randomized, double-blind, placebo-controlled, dose-escalation study was conducted. A total of 56 healthy volunteers received IDP-73152 mesylate in a single oral dose of 40, 80, 160, 320, 640, or 1280 mg in the fasted and fed (640 mg only) states. Blood and urine samples for PK analysis were collected up to 48 h post dose.Results: The area under the plasma concentration-time curve (AUC0-t) of IDP-73152 increased in a dose-proportional manner in the range of 40–320 mg. The mean terminal half-life decreased from 10.7 to 6.2 hrs as the dose increased. The fraction excreted unchanged in the urine ranged from 0.05 to 0.12. In the 640-mg dose group, food delayed the median time to peak concentration (tmax) from 0.9 to 3.5 hrs. Furthermore, the maximum plasma concentration (Cmax) were decreased by 36.2%; however, AUC0-t was not generally affected. No serious adverse event or clinically significant findings were observed.Conclusions: The systemic exposure of IDP-73152 proportionally increased as the dose increased up to 320 mg. The rate of absorption and extent of exposure were reduced by food intake. IDP-73152 was well tolerated without clinically significant adverse effects after a single oral administration.Keywords: phase I, pharmacokinetics, antibiotics, peptide deformylase inhibitor