Browsing by Author "Haibo Li"

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    Phase 2a, open-label, dose-escalating, multi-center pharmacokinetic study of favipiravir (T-705) in combination with oseltamivir in patients with severe influenza
    (2020-12-01) Yeming Wang; Wu Zhong; Alex Salam; Joel Tarning; Qingyuan Zhan; Jian an Huang; Heng Weng; Changqing Bai; Yanhong Ren; Koichi Yamada; Dayan Wang; Qiang Guo; Qiongqiong Fang; Sakurai Tsutomu; Xiaohui Zou; Haibo Li; Annelies Gillesen; Lyndsey Castle; Cheng Chen; Hongyan Li; Jing Zhen; Binghuai Lu; Jun Duan; Liping Guo; Jinfang Jiang; Ruiyuan Cao; Guohui Fan; Jintong Li; Frederick G. Hayden; Chen Wang; Peter Horby; Bin Cao; Chinese Academy of Medical Sciences & Peking Union Medical College; The First Affiliated Hospital of Soochow University; China PLA General Hospital; Fujian Provincial Hospital; Beijing Institute of Pharmacology and Toxicology; Chinese Center for Disease Control and Prevention; University of Virginia School of Medicine; Capital Medical University; Toyama Chemical Co., Ltd.; China-Japan Friendship Hospital; Mahidol University; Nuffield Department of Medicine; HQ Bioscience Co., Ltd.
    © 2020 The Authors Background: The pharmacokinetics and appropriate dose regimens of favipiravir are unknown in hospitalized influenza patients; such data are also needed to determine dosage selection for favipiravir trials in COVID-19. Methods: In this dose-escalating study, favipiravir pharmacokinetics and tolerability were assessed in critically ill influenza patients. Participants received one of two dosing regimens; Japan licensed dose (1600 mg BID on day 1 and 600 mg BID on the following days) and the higher dose (1800 mg/800 mg BID) trialed in uncomplicated influenza. The primary pharmacokinetic endpoint was the proportion of patients with a minimum observed plasma trough concentration (Ctrough) ≥20 mg/L at all measured time points after the second dose. Results: Sixteen patients were enrolled into the low dose group and 19 patients into the high dose group of the study. Favipiravir Ctrough decreased significantly over time in both groups (p <0.01). Relative to day 2 (48 hrs), concentrations were 91.7% and 90.3% lower in the 1600/600 mg group and 79.3% and 89.5% lower in the 1800/800 mg group at day 7 and 10, respectively. In contrast, oseltamivir concentrations did not change significantly over time. A 2-compartment disposition model with first-order absorption and elimination described the observed favipiravir concentration-time data well. Modeling demonstrated that less than 50% of patients achieved Ctrough ≥20 mg/L for >80% of the duration of treatment of the two dose regimens evaluated (18.8% and 42.1% of patients for low and high dose regimen, respectively). Increasing the favipravir dosage predicted a higher proportion of patients reaching this threshold of 20 mg/L, suggesting that dosing regimens of ≥3600/2600 mg might be required for adequate concentrations. The two dosing regimens were well-tolerated in critical ill patients with influenza. Conclusion: The two dosing regimens proposed for uncomplicated influenza did not achieve our pre-defined treatment threshold.
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    Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs
    (2010-03-01) Jianbing Mu; Rachel A. Myers; Hongying Jiang; Shengfa Liu; Stacy Ricklefs; Michael Waisberg; Kesinee Chotivanich; Polrat Wilairatana; Srivicha Krudsood; Nicholas J. White; Rachanee Udomsangpetch; Liwang Cui; May Ho; Fengzhen Ou; Haibo Li; Jianping Song; Guoqiao Li; Xinhua Wang; Suon Seila; Sreng Sokunthea; Duong Socheat; Daniel E. Sturdevant; Stephen F. Porcella; Rick M. Fairhurst; Thomas E. Wellems; Philip Awadalla; Xin Zhuan Su; National Institute of Allergy and Infectious Diseases; University of Montreal; North Carolina State University; Xiamen University; National Institutes of Health, Bethesda; Mahidol University; Pennsylvania State University; University of Calgary; Research Center for Qinghao; Guangzhou University of Traditional Chinese Medicine; National Center for Parasitology, Entomology and Malaria Control
    Antimalarial drugs impose strong selective pressure on Plasmodium falciparum parasites and leave signatures of selection in the parasite genome; screening for genes under selection may suggest potential drug or immune targets. Genome-wide association studies (GWAS) of parasite traits have been hampered by the lack of high-throughput genotyping methods, inadequate knowledge of parasite population history and time-consuming adaptations of parasites to in vitro culture. Here we report the first Plasmodium GWAS, which included 189 culture-adapted P. falciparum parasites genotyped using a custom-built Affymetrix molecular inversion probe 3K malaria panel array with a coverage of 1 SNP per 7 kb. Population structure, variation in recombination rate and loci under recent positive selection were detected. Parasite half-maximum inhibitory concentrations for seven antimalarial drugs were obtained and used in GWAS to identify genes associated with drug responses. This study provides valuable tools and insight into the P. falciparum genome. © 2010 Nature America, Inc. All rights reserved.