Safety, Tolerability, and Pharmacokinetics of Recombinant Human Neuregulin-1 in Healthy Chinese Subjects.
Background: We investigated the safety, tolerability, and pharmacokinetics of intravenous recombinant human Neuregulin-1 (rhNRG-1), a DNA recombinant protein for the treatment of chronic heart failure, in healthy Chinese volunteers following single and multiple dose administration. Methods and Resul...
| Publicado en: | American Journal of Cardiovascular Drugs Vol. 23; no. 4; pp. 419 - 429 |
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| Autores principales: | , , , , , , , , |
| Formato: | research tables/charts randomized controlled trial Journal Article |
| Publicado: |
Springer Nature
Jul2023
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=164782775&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 164782775 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 11753277 G7S jtl: American Journal of Cardiovascular Drugs issn: 11753277 maglogo: N pubinfo: dt: Jul2023 vid: 23 iid: 4 pid: 87227 pub: Springer Nature artinfo: ui: 164782775 163786974 164782775 164782775 10.1007/s40256-023-00585-6 164782775 ppf: 419 ppct: 10 formats: tig: atl: Safety, Tolerability, and Pharmacokinetics of Recombinant Human Neuregulin-1 in Healthy Chinese Subjects. aug: au: Xu, Junyu Sun, Peihong Zhao, Xia Meng, Lei Wang, Xiaorui Qin, Xiaoyan Zhou, Ying Zhou, Mingdong Cui, Yimin affil: Department of Pharmacy, Peking University First Hospital, No.8, Xishiku Street, Xicheng District, 100034, Beijing, People's Republic of China sug: subj: Recombinant Proteins Pharmacokinetics Recombinant Proteins Adverse Effects Growth Substances Nerve Growth Factors Human China Random Assignment Randomized Controlled Trials Patient Safety ab: Background: We investigated the safety, tolerability, and pharmacokinetics of intravenous recombinant human Neuregulin-1 (rhNRG-1), a DNA recombinant protein for the treatment of chronic heart failure, in healthy Chinese volunteers following single and multiple dose administration. Methods and Results: To evaluate the safety and tolerance after single-dosing escalation, 28 subjects were divided into six groups (0.2, 0.4, 0.8, 1.2, 1.6, and 2.4 μg/kg) to receive an intravenous (IV) infusion of rhNRG-1 over 10 min by a randomized, open-label design. Only the 1.2 μg/kg dose group obtained pharmacokinetic parameters: Cmax was 7.645 (24.21) ng/mL, AUC0–t was 97.088 (21.41) min·ng/mL. To assess the safety and pharmacokinetics after multiple-dosing, 32 subjects were divided into four groups (0.2, 0.4, 0.8, and 1.2 μg/kg) to receive a 10-min IV infusion of rhNRG-1 for five consecutive days. After multiple dosing of 1.2 μg/kg, the Cmax value at day 5 was 8.838 (51.6) ng/mL and the AUC0–t value at day 5 was 109.890 (32.99) min·ng/mL. RhNRG-1 is rapidly cleared from the blood and has a short t1/2 of about 10 min. The adverse events related to rhNRG-1 mainly included flat or inverted T wave and gastrointestinal reactions, all of which were mild. Conclusions: It is concluded that rhNRG-1 is safe and well tolerated in healthy Chinese subjects at the dosing levels used in this study. The severity and frequency of adverse events did not increase with the prolongation of administration time. Clinical Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn) Identifier No. ChiCTR2000041107. pubtype: Academic Journal doctype: research tables/charts randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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