First human study of the investigational sedative and anesthetic drug AZD3043: A dose-escalation trial to assess the safety, pharmacokinetics, and efficacy of a 30-minute infusion in healthy male volunteers

Anesthesia and Analgesia

Volumn 121, Issue 4, 2015, Pages 885-893

  Kalman, Sigridur ^a,b   Koch, Pauline ^a,b   Ahlén, Kjell ^c   Kanes, Stephen J ^d   Barassin, Stéphane ^c   Björnsson, Marcus A ^c,e   Norberg, Åke ^a,b  

^a KAROLINSKA INSTITUTE   (Sweden)

^b KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^c ASTRAZENECA R AND D   (Sweden)

^d ASTRAZENECA   (United Kingdom)

^e Department of Clinical Pharmacology and Pharmacometrics and Pharmetheus AB   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

AZD 3043; DRUG METABOLITE; THRX 108893; UNCLASSIFIED DRUG; 4 AMINOBUTYRIC ACID A RECEPTOR; AZD-3043; HYPNOTIC SEDATIVE AGENT; NEW DRUG; PHENYLACETIC ACID DERIVATIVE;

ADULT; ANESTHESIA LEVEL; AREA UNDER THE CURVE; ARTERIAL OXYGEN SATURATION; ARTERIAL PRESSURE; ARTICLE; BISPECTRAL INDEX; BLOOD GAS; BREATHING RATE; COHORT ANALYSIS; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DYSPNEA; ERYTHEMA; HEADACHE; HUMAN; HUMAN EXPERIMENT; INFUSION RATE; INJECTION SITE PAIN; LIMIT OF QUANTITATION; LOUDNESS RECRUITMENT; MALE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MUSCLE TONE; NAUSEA; NAUSEA AND VOMITING; NORMAL HUMAN; OPEN STUDY; PHASE 1 CLINICAL TRIAL; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; PROPRIOCEPTION; RESTLESSNESS; SEDATION; SINGLE DRUG DOSE; THORAX PAIN; TREATMENT DURATION; VITAL SIGN; ADOLESCENT; CHEMICALLY INDUCED; CLINICAL TRIAL; DRUG EFFECTS; INTRAVENOUS DRUG ADMINISTRATION; TIME; TREATMENT OUTCOME; YOUNG ADULT;

ADOLESCENT; ADULT; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUGS, INVESTIGATIONAL; ERYTHEMA; HEADACHE; HEALTHY VOLUNTEERS; HUMANS; HYPNOTICS AND SEDATIVES; INFUSIONS, INTRAVENOUS; MALE; PHENYLACETATES; RECEPTORS, GABA-A; TIME FACTORS; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84941902117     PISSN: 00032999     EISSN: 15267598     Source Type: Journal    
DOI: 10.1213/ANE.0000000000000831     Document Type: Article

References (21)

1. Bailey PL, Pace NL, Ashburn MA, Moll JW, East KA, Stanley TH. Frequent hypoxemia and apnea after sedation with midazolam and fentanyl. Anesthesiology 1990;73:826-30
2. Miner JR, Biros M, Krieg S, Johnson C, Heegaard W, Plummer D. Randomized clinical trial of propofol versus methohexital for procedural sedation during fracture and dislocation reduction in the emergency department. Acad Emerg Med 2003;10:931-7
3. Win NN, Fukayama H, Kohase H, Umino M. The different effects of intravenous propofol and midazolam sedation on hemodynamic and heart rate variability. Anesth Analg 2005;101:97-102
4. Tan CH, Onsiong MK. Pain on injection of propofol. Anaesthesia 1998;53:468-76
5. Sneyd JR, Rigby-Jones AE. New drugs and technologies, intravenous anaesthesia is on the move (again). Br J Anaesth 2010;105:246-54
6. Albanese J, Martin C, Lacarelle B, Saux P, Durand A, Gouin F. Pharmacokinetics of long-term propofol infusion used for sedation in ICU patients. Anesthesiology 1990;73:214-7
7. Shafer A. Complications of sedation with midazolam in the intensive care unit and a comparison with other sedative regimens. Crit Care Med 1998;26:947-56
8. Egan TD. Is anesthesiology going soft? Trends in fragile pharmacology. Anesthesiology 2009;111:229-30
9. Egan TD, Obara S, Jenkins TE, Jaw-Tsai SS, Amagasu S, Cook DR, Steffensen SC, Beattie DT. AZD-3043: a novel, metabolically labile sedative-hypnotic agent with rapid and predictable emergence from hypnosis. Anesthesiology 2012;116:1267-77
10. Tramèr MR, Moore RA, McQuay HJ. Propofol and bradycardia: causation, frequency and severity. Br J Anaesth 1997;78:642-51
11. Fridericia LS. The duration of systole in an electrocardiogram in normal humans and in patients with heart disease. 1920. Ann Noninvasive Electrocardiol 2003;8:343-51
12. Chernik DA, Gillings D, Laine H, Hendler J, Silver JM, Davidson AB, Schwam EM, Siegel JL. Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol 1990;10:244-51
13. Björnsson MA, Norberg A, Kalman S, Simonsson USH. A recirculatory model for pharmacokinetics and the effects on bispectral index after intravenous infusion of the sedative and anesthetic AZD3043 in healthy volunteers. Anesth Analg 2015;121:904-13
14. Miner JR, Danahy M, Moch A, Biros M. Randomized clinical trial of etomidate versus propofol for procedural sedation in the emergency department. Ann Emerg Med 2007;49:15-22
15. Reddy RV, Moorthy SS, Dierdorf SF, Deitch RD Jr, Link L. Excitatory effects and electroencephalographic correlation of etomidate, thiopental, methohexital, and propofol. Anesth Analg 1993;77:1008-11
16. Sneyd JR, Wright PM, Cross M, Thompson P, Voortman G, Weideman MM, Andrews CJ, Daniell CJ. Administration to humans of ORG 21465, a water soluble steroid i.v. anaesthetic agent. Br J Anaesth 1997;79:427-32
17. Sear JW. ORG 21465, a new water-soluble steroid hypnotic: more of the same or something different? Br J Anaesth 1997;79:417-9
18. Walder B, Tramèr MR, Seeck M. Seizure-like phenomena and propofol: a systematic review. Neurology 2002;58:1327-32
19. Voss LJ, Sleigh JW, Barnard JP, Kirsch HE. The howling cortex: seizures and general anesthetic drugs. Anesth Analg 2008;107:1689-703
20. Punjasawadwong Y, Boonjeungmonkol N, Phongchiewboon A. Bispectral index for improving anaesthetic delivery and postoperative recovery. Cochrane Database Syst Rev 2007;4:CD003843
21. Glass PS, Bloom M, Kearse L, Rosow C, Sebel P, Manberg P. Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers. Anesthesiology 1997;86:836-47