A Phase 1, Single-center, Double-blind, Placebo-controlled Study in Healthy Subjects to Assess the Safety, Tolerability, Clinical Effects, and Pharmacokinetics-Pharmacodynamics of Intravenous Cyclopropyl-methoxycarbonylmetomidate (ABP-700) after a Single Ascending Bolus Dose

Anesthesiology

Volumn 127, Issue 1, 2017, Pages 20-35

  Struys, Michel M R F ^a,b   Valk, Beatrijs I ^a   Eleveld, Douglas J ^a   Absalom, Anthony R ^a   Meyer, Peter ^a   Meier, Sascha ^a   Den Daas, Izaak ^c   Chou, Thomas ^d   Van Amsterdam, Kai ^a   Campagna, Jason A ^e   Sweeney, Steven P ^e  

^a UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^b GHENT UNIVERSITY   (Belgium)

^c QPS Netherlands BV   (Netherlands)

^d QPS LLC   (United States)

^e MEDICINES COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABP 700; ANESTHETIC AGENT; CORTICOTROPIN; HYDROCORTISONE; PLACEBO; UNCLASSIFIED DRUG; ETOMIDATE; HYPNOTIC SEDATIVE AGENT;

ADULT; ANESTHESIA COMPLICATION; APNEA; ARTICLE; BISPECTRAL INDEX; BLOOD SAMPLING; BODY MASS; CLINICAL LABORATORY; COHORT ANALYSIS; CONTROLLED STUDY; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG SAFETY; DRUG SCREENING; DRUG TOLERABILITY; ELEVATED BLOOD PRESSURE; END TIDAL CARBON DIOXIDE TENSION; EYE DISEASE; FATIGUE; FEMALE; FOLLOW UP; HEADACHE; HICCUP; HUMAN; HYPERVENTILATION; INCIDENCE; INJECTION SITE PAIN; LABORATORY TEST; MAJOR CLINICAL STUDY; MALE; MAXIMUM TOLERATED DOSE; MEAN ARTERIAL PRESSURE; MEDICAL HISTORY; MUSCLE SPASM; MUSCLE TWITCH; MYOCLONUS; NAUSEA AND VOMITING; OXYGEN SATURATION; PATIENT MONITORING; PHYSICAL EXAMINATION; PRESYNCOPE; PRIORITY JOURNAL; RESPIRATORY TRACT DISEASE; RESTLESSNESS; SINGLE DRUG DOSE; SINUS TACHYCARDIA; ADOLESCENT; ANALOGS AND DERIVATIVES; CLINICAL TRIAL; DOUBLE BLIND PROCEDURE; INTRAVENOUS DRUG ADMINISTRATION; MIDDLE AGED; PHASE 1 CLINICAL TRIAL; REFERENCE VALUE; YOUNG ADULT;

ADOLESCENT; ADULT; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; ETOMIDATE; FEMALE; HUMANS; HYPNOTICS AND SEDATIVES; INFUSIONS, INTRAVENOUS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; REFERENCE VALUES; YOUNG ADULT;

EID: 85020942163     PISSN: 00033022     EISSN: 15281175     Source Type: Journal    
DOI: 10.1097/ALN.0000000000001662     Document Type: Article

References (29)

1. Campagna JA, Pojasek K, Grayzel D, Randle J, Raines DE: Advancing novel anesthetics: Pharmacodynamic and pharmacokinetic studies of cyclopropyl-methoxycarbonyl metomidate in dogs. ANESTHESIOLOGY 2014; 121:1203-16
2. Husain SS, Pejo E, Ge R, Raines DE: Modifying methoxycarbonyl etomidate inter-ester spacer optimizes in vitro metabolic stability and in vivo hypnotic potency and duration of action. ANESTHESIOLOGY 2012; 117:1027-36
3. Sneyd JR, Rigby-Jones AE: New drugs and technologies, intravenous anaesthesia is on the move (again). Br J Anaesth 2010; 105:246-54
4. Johnson KB: New horizons in sedative hypnotic drug development: Fast, clean, soft. Anesth Analg 2012; 115:220-2
5. Forman SA: Clinical and molecular pharmacology of etomidate. ANESTHESIOLOGY 2011; 114:695-707
6. Wagner RL, White PF, Kan PB, Rosenthal MH, Feldman D: Inhibition of adrenal steroidogenesis by the anesthetic etomidate. N Engl J Med 1984; 310:1415-21
7. Pejo E, Ge R, Banacos N, Cotten JF, Husain SS, Raines DE: Electroencephalographic recovery, hypnotic emergence, the effects of metabolite after continuous infusions of a rapidly metabolized etomidate analog in rats. ANESTHESIOLOGY 2012; 116:1057-65
8. Zhang L, Beal SL, Sheinerz LB: Simultaneous vs. sequential analysis for population PK/PD data II: Robustness of methods. J Pharmacokinet Pharmacodyn 2003; 30:405-16
9. Zhang L, Beal SL, Sheiner LB: Simultaneous vs. sequential analysis for population PK/PD data I: Best-case performance. J Pharmacokinet Pharmacodyn 2003; 30:387-404
10. Varvel JR, Donoho DL, Shafer SL: Measuring the predictive performance of computer-controlled infusion pumps. J Pharmacokinet Biopharm 1992; 20:63-94
11. Doenicke AW, Roizen MF, Kugler J, Kroll H, Foss J, Ostwald P: Reducing myoclonus after etomidate. ANESTHESIOLOGY 1999; 90:113-9
12. Hüter L, Schreiber T, Gugel M, Schwarzkopf K: Low-dose intravenous midazolam reduces etomidate-induced myoclonus: A prospective, randomized study in patients undergoing elective cardioversion. Anesth Analg 2007; 105:1298-302, table of contents
13. Joint National Committee on Prevention, Treatment of High Blood Pressure: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, Treatment of High Blood Pressure. Bethesda, National Heart, Lung, Blood Institute, 2004, pp 54
14. Dahaba AA: Different conditions that could result in the Bispectral Index indicating an incorrect hypnotic state. Anesth Analg 2005; 101:765-73
15. Ge R, Pejo E, Gallin H, Jeffrey S, Cotten JF, Raines DE: The pharmacology of cyclopropyl-methoxycarbonyl metomidate: A comparison with propofol. Anesth Analg 2014; 118:563-7
16. Ghoneim MM, Yamada T: Etomidate: A clinical and electroencephalographic comparison with thiopental. Anesth Analg 1977; 56:479-85
17. Schnider TW, Minto CF, Shafer SL, Gambus PL, Andresen C, Goodale DB, Youngs EJ: The influence of age on propofol pharmacodynamics. ANESTHESIOLOGY 1999; 90:1502-16
18. Pilge S, Zanner R, Schneider G, Blum J, Kreuzer M, Kochs EF: Time delay of index calculation: Analysis of cerebral state, Bispectral, narcotrend indices. ANESTHESIOLOGY 2006; 104:488-94
19. Gooding JM, Corssen G: Etomidate: An ultrashort-acting nonbarbiturate agent for anesthesia induction. Anesth Analg 1976; 55:286-9
20. Walder B, Tramèr MR, Seeck M: Seizure-like phenomena and propofol: A systematic review. Neurology 2002; 58:1327-32
21. Kalman S, Koch P, Ahlén K, Kanes SJ, Barassin S, Björnsson MA, Norberg Å: First human study of the investigational sedative and anesthetic drug AZD3043: A dose-escalation trial to assess the safety, pharmacokinetics, efficacy of a 30-minute infusion in healthy male volunteers. Anesth Analg 2015; 121:885-93
22. Li Y, Flood P, Cornes S: Electroencephalography of seizurelike movements during general anesthesia with propofol: Seizures or nonepileptic events? A A Case Rep 2015; 5:195-8
23. Gooding JM, Corssen G: Effect of etomidate on the cardiovascular system. Anesth Analg 1977; 56:717-9
24. Ebert TJ, Muzi M: Sympathetic hyperactivity during desflurane anesthesia in healthy volunteers. A comparison with isoflurane. ANESTHESIOLOGY 1993; 79:444-53
25. Choi SD, Spaulding BC, Gross JB, Apfelbaum JL: Comparison of the ventilatory effects of etomidate and methohexital. ANESTHESIOLOGY 1985; 62:442-7
26. Blouin RT, Conard PF, Gross JB: Time course of ventilatory depression following induction doses of propofol and thiopental. ANESTHESIOLOGY 1991; 75:940-4
27. Hermann DJ, Egan TD, Muir KT: Influence of arteriovenous sampling on remifentanil pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 1999; 65:511-8
28. Schnider TW, Minto CF, Gambus PL, Andresen C, Goodale DB, Shafer SL, Youngs EJ: The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers. ANESTHESIOLOGY 1998; 88:1170-82
29. Bruhn J, Myles PS, Sneyd R, Struys MM: Depth of anaesthesia monitoring: What's available, what's validated and what's next? Br J Anaesth 2006; 97:85-94