Pharmacokinetics and pharmacodynamics of the short-acting sedative CNS 7056 in sheep

British Journal of Anaesthesia

Volumn 105, Issue 6, 2010, Pages 798-809

  Upton, R N ^a   Somogyi, A A ^a   Martinez, A M ^a   Colvill, J ^a   Grant, C ^a  

^a UNIVERSITY OF ADELAIDE   (Australia)

Author keywords

benzodiazepine; cardiac output; CNS 7056; pharmacodynamics; pharmacokinetics; sedation; sheep

Indexed keywords

ALPRAZOLAM; BENZODIAZEPINE DERIVATIVE; CNS 7054; CNS 7056; DIAZEPAM; ICE; SEDATIVE AGENT; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; BLOOD SAMPLING; COMPARTMENT MODEL; DRUG CLEARANCE; DRUG HALF LIFE; ELECTROENCEPHALOGRAM; EX VIVO STUDY; FEMALE; HEART OUTPUT; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PHARMACODYNAMICS; PHARMACOKINETICS; PRIORITY JOURNAL; SEDATION; SHEEP; TIME TO MAXIMUM PLASMA CONCENTRATION;

EID: 78649456563     PISSN: 00070912     EISSN: 14716771     Source Type: Journal    
DOI: 10.1093/bja/aeq260     Document Type: Article

References (19)

1. Kilpatrick GJ, McIntyre MS, Cox RF, et al. CNS 7056: a novel ultra-short-acting benzodiazepine. Anesthesiology 2007; 107: 60-6
2. Upton RN, Martinez AM, Grant C. A dose escalation study in sheep of the effects of the benzodiazepine CNS 7056 on sedation, the EEG, and the respiratory and cardiovascular systems. Br J Pharmacol 2008; 155: 52-61
3. Upton RN, Martinez AM, Grant C. Comparison of the sedative properties of CNS 7056, midazolam, and propofol in sheep. Br J Anaesth 2009; 103: 848-57
4. Georgita C, Albu F, David V, Medvedovici A. Nonlinear calibrations on the assay of dilitiazem and two of its metabolites from plasma samples by means of liquid chromatography and ESI/MS detection: application to a bioequivalence study. Biomed Chromatogr 2008; 22: 289-97
5. Upton R, Grant C, Ludbrook G. An ultrasonic Doppler venous outflow method for the continuous measurement of cerebral blood flow in conscious sheep. J Cereb Blood Flow Metab 1994; 14: 680-8
6. Doolette DJ, Upton RN, Grant C. Agreement between ultrasonic Doppler venous outflow and Kety and Schmidt estimates of cerebral blood flow. Clin Exp Pharmacol Physiol 1999; 26: 736-40
7. R Development Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing, 2005
8. Gabrielsson J, Weiner D. Pharmacokinetic and Pharmacokinetic Data Analysis: Concepts and Applications, 3rd Edn. Stockholm: Swedish Pharmaceutical Press, 2000
9. Bergstrand M, Karlsson MO. Handling data below the limit of quantification in mixed effect models. AAPS J 2009; 11: 371-80
10. Venables WN, Ripley BD. Modern Applied Statistics with S-plus, 4th Edn. Germany: Springer, 2002
11. Shafer SL, Struys MM. Mixed effect modeling in analgesia trials. Anesth Analg 2008; 107: 9-10
12. Upton RN. Relationships between steady state blood concentrations and cardiac output during intravenous infusions. Bio-pharm Drug Dispos 2000; 21: 69-76
13. Upton RN, Ludbrook GL, Grant C, Martinez AM. Cardiac output is a determinant of the initial concentrations of propofol after short-infusion administration. Anesth Analg 1999; 89: 545-52
14. Kuipers JA, Boer F, Olofsen E, et al. Recirculatory and compart-mental pharmacokinetic modeling of alfentanil in pigs: the influence of cardiac output. Anesthesiology 1999; 90: 1146-57
15. Minto CF, Schnider TW. Contributions of PK/PD modeling to intravenous anesthesia. Clin Pharmacol Ther 2008; 84: 27-38
16. Jamei M, Dickinson GL, Rostami-Hodjegan A. A framework for assessing inter-individual variability in pharmacokinetics using virtual human populations and integrating general knowledge of physical chemistry, biology, anatomy, physiology and genetics: a tale of 'bottom-up' vs 'top-down' recognition of covariates. Drug Metab Pharmacokinet 2009; 24: 53-75
17. Bailey JM. Context-sensitive half-times: what are they and how valuable are they in anaesthesiology? Clin Pharmacokinet 2002; 41: 793-9
18. Upton RN. Organ weights and blood flows of sheep and pig for physiological pharmacokinetic modelling. J Pharmacol Toxicol Methods 2008; 58: 198-205
19. Sneyd JR, Rigby-Jones AE. New drugs and technologies, intravenous anaesthesia is on the up (again). Br J Anaesth 2010; 105: 246-54