https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/118 Sat, 04 Apr 2026 00:50:01 GMT 2026-04-04T00:50:01Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/63392 Title: Pharmacokinetics and safety of candidate tocilizumab biosimilar CT-P47 versus reference tocilizumab: a randomized, double-blind, single-dose phase I study Authors: Yu, Kyung-Sang; Kim, Byungwook; Shin, Dongseong; Park, Min Kyu; Hwang, Jun Gi; Kim, Min-Gul; Chung, Hyewon; Ghim, JongLyul; Chung, Jae-Yong; Smolen, Josef S.; Burmester, Gerd R.; Kim, SungHyun; Bae, YunJu; Jeon, DaBee; Yoo, JaeKyoung; Yang, GoEun; Bae, JiHun; Keystone, Edward Abstract: Background CT-P47 is a candidate tocilizumab biosimilar. This study assessed the pharmacokinetic (PK) equivalence of CT-P47 and European Union-approved reference tocilizumab (EU-tocilizumab) in healthy Asian adults. Research design and methods This double-blind, multicenter, parallel-group trial randomized healthy adults (1:1) to receive a single (162 mg/0.9 mL) subcutaneous dose of CT-P47 or EU-tocilizumab. The primary endpoint (Part 2) was PK equivalence by area under the concentration – time curve (AUC) from time zero to last quantifiable concentration (AUC0–last), AUC from time zero to infinity (AUC0–inf), and maximum serum concentration (Cmax). PK equivalence was concluded if 90% confidence intervals (CIs) for the ratios of geometric least-squares means (gLSMs) were within the 80–125% equivalence margin. Additional PK endpoints, immunogenicity, and safety were evaluated. Results In Part 2, 289 participants were randomized (146 CT-P47; 143 EU-tocilizumab); 284 received study drug. AUC0–last, AUC0–inf, and Cmax were equivalent between CT-P47 and EU-tocilizumab: 90% CIs for the ratios of gLSMs were within the 80–125% equivalence margin. Secondary PK endpoints, immunogenicity, and safety were comparable between groups. Conclusions CT-P47 demonstrated PK equivalence with EU-tocilizumab and was well tolerated, following a single dose in healthy adults. Clinical trial registration www.clinicaltrials.gov identifier is NCT05188378. Mon, 01 May 2023 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/63392 2023-05-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/62604 Title: Effects of Simvastatin on Pharmacokinetics and Anticoagulant Effects of Dabigatran in Healthy Subjects Authors: Chung, Hyewon; Kim, Jong-Min; Park, Jin-Woo; Noh, Jihyeon; Kim, Kyoung-Ah; Park, Ji-Young Abstract: Higher risk of major hemorrhage associated with concomitant use of dabigatran and simvastatin compared to other statins was previously reported with a suggestion of P-glycoprotein-mediated interaction. The aim of this study was to evaluate the effects of simvastatin on pharmacokinetics and anticoagulant effects of dabigatran, a direct oral anticoagulant. A total of 12 healthy subjects were enrolled in an open-label, two-period, single sequence study. Subjects were given 150 mg of dabigatran etexilate followed by 40 mg of once-daily simvastatin for seven days. Dabigatran etexilate was administered with simvastatin on the seventh day of simvastatin administration. Blood samples for pharmacokinetic and pharmacodynamic analyses were obtained until 24 h post-dose of dabigatran etexilate with or without co-administration of simvastatin. Pharmacokinetic parameters were derived from noncompartmental analysis for dabigatran etexilate, dabigatran, and dabigatran acylglucuronide. When simvastatin was co-administered, geometric mean ratios of area under time-concentration curves for dabigatran etexilate, dabigatran, and dabigatran acylglucuronide were 1.47, 1.21, and 1.57, respectively, compared to when dabigatran etexilate was administered alone. Thrombin generation assay and coagulation assay showed similar profiles between before and after co-administration of simvastatin. This study provides evidence that simvastatin treatment plays a minor role in modulating pharmacokinetics and anticoagulant effects of dabigatran etexilate. Wed, 01 Mar 2023 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/62604 2023-03-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/62108 Title: Gene Dose-Dependent and Additive Effects of ABCG2 rs2231142 and SLC2A9 rs3733591 Genetic Polymorphisms on Serum Uric Acid Levels Authors: Park, Jin-Woo; Noh, Ji-Hyeon; Kim, Jong-Min; Lee, Hwa-Young; Kim, Kyoung-Ah; Park, Ji-Young Abstract: This study aimed to evaluate whether the single nucleotide polymorphisms of ATP-binding cassette subfamily G member 2 (ABCG2) and solute carrier family 2 member 9 (SLC2A9) affect individual blood uric acid levels using pyrosequencing. ABCG2 (rs2231142, rs72552713, rs2231137), SLC2A9 (rs3734553, rs3733591, rs16890979), and individual uric acid levels were prospectively analyzed in 250 healthy young Korean male participants. Prominent differences in uric acid levels of the alleles were observed in the SLC2A9 rs3733591 polymorphism: wild-type (AA) vs. heterozygote (AG), 0.7 mg/dL (p < 0.0001); AA vs. mutant type (GG), 1.32 mg/dL (p < 0.0001); and AG vs. GG, 0.62 mg/dL (p < 0.01). In ABCG2 single nucleotide polymorphisms (SNPs), the statistically significant differences in uric acid levels were only found in rs2231142 between CC vs. AA (1.06 mg/dL; p < 0.001), and CC vs. CA (0.59 mg/dL; p < 0.01). Serum uric acid levels based on the ABCG2 and SLC2A9 diplotype groups were also compared. The uric acid levels were the lowest in the CC/AA diplotype and highest in the AA/AG diplotype. In addition, the SNP SLC2A9 rs3733591 tended to increase the uric acid levels when the ABCG2 rs2231142 haplotypes were fixed. In conclusion, both the ABCG2 rs2231142 and SLC2A9 rs3733591 polymorphisms may additively elevate blood uric acid levels. Thu, 01 Dec 2022 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/62108 2022-12-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/61765 Title: Ocular Distribution and Pharmacokinetics of 8-Oxo-2'-Deoxyguanosine: A Novel Therapeutic Candidate of Ocular Surface Diseases Authors: Chung, Hyewon; Ha, Yuseung; Kim, Yong Ho; Kim, Dong Hyun; Shin, Dongseong Abstract: Purpose: This study evaluated the ocular distribution and plasma pharmacokinetics (PKs) of 8-oxo-2′-deoxyguanosine (8-oxo-dG) in rabbits and rats, respectively. Methods: A test formulation containing radiolabeled [14 C]8-oxo-dG and unlabeled 8-oxo-dG was ocularly administered to rabbits as a single dose of 1 mg per body and intravenously injected to rats as a single dose of 5 mg/kg. The ocular distribution of [14 C]8-oxo-dG was evaluated using autoradiography until 48 h postdose. Plasma radioactivity in rabbits and rats was determined until 72 and 168 h, respectively. Results: After ocular instillation, [14 C]8-oxo-dG distributed into ocular tissues, and high radioactivity concentrations were observed in the ciliary body, conjunctiva, and cornea. The maximum plasma concentration (Cmax) and area under the concentration–time curve (AUC0-t) were highest in the ciliary body and conjunctiva, respectively. In the conjunctiva, cornea, and aqueous humor, time to reach Cmax (Tmax) was 0.5 h, and the half-lives were 11.2, 30.2, and 15.1 h, respectively. The radioactivity of [14 C]8-oxo-dG in plasma of rabbits displayed a double-peak phenomenon with the second peak considered as Cmax (37.9 ± 3.1 ng eq./mL) occurring 24 h postdose. After systemic exposure of [14 C]8-oxo-dG in rats, a rapid decline in the initial phase and a terminal half-life of 56.1 ± 31.3 h were observed. Conclusions: Rapid ocular distribution and high concentrations in anterior ocular tissues with minimal systemic exposure were observed after the ocular instillation of 8-oxo-dG in rabbits. These PK profiles are favorable for the treatment of ocular surface diseases. Sat, 01 Oct 2022 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/61765 2022-10-01T00:00:00Z