دورية أكاديمية
Dose-response and Cardiopulmonary Side Effects of the Novel Neuromuscular-blocking Drug CW002 in Man.
| العنوان: | Dose-response and Cardiopulmonary Side Effects of the Novel Neuromuscular-blocking Drug CW002 in Man. |
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| المؤلفون: | Heerdt PM; From the Department of Anesthesiology, Yale Medical School, New Haven, Connecticut (P.M.H.); Department of Anesthesiology, Weill Cornell Medical College, New York, New York (H.S., M.T.M., J.K.M., D.G., M.S., P.S., J.J.S., C.A.L.); and School of Pharmacy, Union University, Jackson, Tennessee (J.S.O.)., Sunaga H, Owen JS, Murrell MT, Malhotra JK, Godfrey D, Steinkamp M, Savard P, Savarese JJ, Lien CA |
| المصدر: | Anesthesiology [Anesthesiology] 2016 Dec; Vol. 125 (6), pp. 1136-1143. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 1300217 Publication Model: Print Cited Medium: Internet ISSN: 1528-1175 (Electronic) Linking ISSN: 00033022 NLM ISO Abbreviation: Anesthesiology Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Philadelphia Pa : Lippincott Williams & Wilkins Original Publication: Philadelphia : American Society of Anesthesiologists |
| مواضيع طبية MeSH: | Blood Pressure/*drug effects , Heart Rate/*drug effects , Isoquinolines/*pharmacology , Neuromuscular Blockade/*methods , Neuromuscular Nondepolarizing Agents/*pharmacology , Respiration/*drug effects, Adolescent ; Adult ; Dose-Response Relationship, Drug ; Female ; Histamine Release/drug effects ; Humans ; Male ; Middle Aged ; Young Adult |
| مستخلص: | Background: CW002 is a benzylisoquinolinium nondepolarizing neuromuscular-blocking drug found to be inactivated by cysteine in preclinical studies. The current study represents a dose escalation clinical trial designed to describe CW002 potency, duration, cardiopulmonary side effects, and histamine release. Methods: Healthy subjects anesthetized with sevoflurane/nitrous oxide were divided into five groups (n = 6), each receiving a fixed CW002 dose (0.02, 0.04, 0.06, 0.08, or 0.10 mg/kg), and one group (n = 4) receiving 0.14 mg/kg. Blood pressure and heart rate were continuously recorded along with airway dynamic compliance. Neuromuscular blockade was assessed with mechanomyography at the adductor pollicis. Arterial blood was obtained before and after CW002 injection for analysis of plasma histamine concentration. Potency was estimated from a baseline sigmoid Emax model. Results: ED50 was found to be 0.036 mg/kg (95% CI, 0.020 to 0.053 mg/kg) and ED95 0.077 mg/kg (95% CI, 0.044 to 0.114 mg/kg). At 0.14 mg/kg (1.8 × ED95), 80% twitch depression occurred in 94 ± 18 s with complete block in 200 ± 87 s. Clinical recovery (25% of maximum twitch) occurred in 34 ± 3.4 min, with a 5 to 95% recovery interval of 35.0 ± 2.7 min. The time to a train-of-four ratio greater than 0.9 ranged from 59 to 86 min. CW002 did not elicit histamine release or significant (greater than 10%) changes in blood pressure, heart rate, or dynamic airway compliance. Conclusions: In healthy subjects receiving sevoflurane/nitrous oxide, CW002 at 1.8 × estimated ED95 produces a clinical duration less than 40 min, elicits no histamine release, and has minimal cardiopulmonary side effects. |
| المشرفين على المادة: | 0 (CW 002) 0 (Isoquinolines) 0 (Neuromuscular Nondepolarizing Agents) |
| تواريخ الأحداث: | Date Created: 20161018 Date Completed: 20170609 Latest Revision: 20220317 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1097/ALN.0000000000001386 |
| PMID: | 27749289 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1528-1175 |
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| DOI: | 10.1097/ALN.0000000000001386 |