Objective: Sirukumab (CNTO 136) is a human mAb with high affinity and specificity for binding to interleukin-6. This Phase 1 study evaluated the pharmacokinetics, immunogenicity, safety, and tolerability of sirukumab following a single subcutaneous (s.c.) administration in healthy male Japanese and Caucasian subjects.
Methods: Japanese and Caucasian subjects were randomized to placebo or 25, 50, or 100 mg sirukumab. Blood samples were collected to measure serum sirukumab concentration and antibodies to sirukumab. Noncompartmental analysis and population pharmacokinetic modeling were conducted to characterize sirukumab pharmacokinetics. Adverse events were monitored at each visit.
Results: 25 Japanese and 24 Caucasian subjects received sirukumab and were included in the pharmacokinetic evaluation. Mean Cmax and AUC0-∞of sirukumab increased in an approximately dose-proportional manner in both Japanese and Caucasian subjects. Median tmax was 3 -5 days after s.c. administration of sirukumab. Mean t1/2 was 15 -16 days in Japanese and 15 -18 days in Caucasian subjects. A one-compartment population pharmacokinetic model adequately described sirukumab pharmacokinetics following s.c. administration. The estimated population means for CL/F, V/F, and Ka were 0.54 ±0.03 l/day, 12.2 ±0.55 l, and 0.77 ±0.07 day-1, respectively. Race was not a significant covariate on CL/F or V/F. No subject was positive for antibodies to sirukumab. Adverse events were generally mild and did not appear to be dose-related or lead to study discontinuation.
Conclusions: Sirukumab pharmacokinetics following subcutaneous administration was linear at doses ranging 25 -100 mg and was comparable between Japanese and Caucasian subjects. A single subcutaneous administration of 25, 50, or 100 mg sirukumab appeared to be well tolerated by both Japanese and Caucasian healthy male subjects.
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http://dx.doi.org/10.5414/CP201785 | DOI Listing |
BMC Pregnancy Childbirth
December 2024
Department of Behavioral and Social Sciences, Brown University School of Public Health, Providence, RI, USA.
Background: Gestational Diabetes Mellitus (GDM) affects between 2 and 10% of pregnancies in the United States, with trends of increasing prevalence and a significant amount of variability across race and ethnicity, maternal age, and insurance status. Asian and Native Hawaiian or Other Pacific Islanders (NHOPI) have been documented to have a higher prevalence and risk of developing GDM compared to non-Hispanic white populations and have been under-studied in health disparities research.
Methods: Using data from the Pregnancy Risk Assessment Monitoring System (PRAMS) 2016-2022 surveys, we conducted analyses for the overall PRAMS sample as well as within-group analyses among participants who identify as Asian and NHOPI to identify risk factors for GDM.
Transl Psychiatry
December 2024
Department of Human Anatomy & Histoembryology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Basal ganglia is proposed to mediate symptoms underlying bipolar disorder (BD). To understand the cell type-specific gene expression and network changes of BD basal ganglia, we performed single-nucleus RNA sequencing of 30,752 nuclei from caudate, putamen, globus pallidus, and substantia nigra of control human postmortem brain and 24,672 nuclei from BD brain. Differential expression analysis revealed major difference lying in caudate, with BD medium spiny neurons (MSNs) expressing significantly higher PDE5A, a cGMP-specific phosphodiesterase.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
School of Horticulture, Anhui Agricultural University, Hefei 230036, China.
Iron (Fe) deficiency poses a major threat to pear ( spp.) fruit yield and quality. The () plays a vital part in plant stress responses.
View Article and Find Full Text PDFNutrients
November 2024
Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
Background: Female reproductive aging remains irreversible. More evidence is needed on how polyunsaturated fatty acids (PUFAs) affect the female reproductive lifespan.
Objectives: To identify and validate specific PUFAs that can influence the timing of menarche and menopause in women.
JAMA Netw Open
December 2024
Department of Psychology, Fordham University, Bronx, New Jersey.
Importance: Although racial and ethnic disparities are well documented in children's mean levels of sleep, particularly duration, evidence is mixed for sleep variability, an important sleep dimension of growing interest. Most research has also focused on comparisons of Black and White children, with limited attention to sleep variability disparities among other racially and ethnically minoritized groups such as Asian, Latinx, and multiracial children.
Objective: To investigate racial and ethnic disparities in children's mean levels of sleep and variability of sleep across multiple dimensions and diverse racial and ethnic groups using actigraphy data.
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