caa a22 4500 477126804 CHVBK 20180405111652.0 cr unu---uuuuu 170330e19971201xx s 000 0 eng 10.1023/A:1012156502624 doi (NATIONALLICENCE)springer-10.1023/A:1012156502624 The Pharmacokinetics and Electroencephalogram Response of Remifentanil Alone and in Combination with Esmolol in the Rat [Elektronische Daten] [Sam Haidar, J. Moreton, Zhongming Liang, John Hoke, Keith Muir, Natalie Eddington] Purpose. The goal of this study was to determine if the co-administration of esmolol (ES), a short acting cardioselective β-blocker, significantly alters the pharmacokinetics and/or pharmacodynamics of remifentanil (REMI), an ultra short-acting opioid, in the rat. Methods. Sprague-Dawley rats (N = 8, Wt. = 325 ± 15g) were surgically implanted with stainless steel cerebrocortical EEG electrodes three days before the study. Each rat was dosed with REMI (15 μg/ kg/min), and REMI & ES (15 μg/kg/min and 600 μg/kg/min) for 21 minutes in a random crossover design. Six serial blood samples were collected over 25 minutes into test-tubes containing 0.5ml acetonitrile. Blood samples were extracted with methylene chloride and analyzed by a validated GC-MS assay. EEG was captured and subjected to power spectral analysis (0.1−50 Hz) for spectral edge (97%). Results. No significant differences (p < 0.05) were found in clearance (REMI = 287 + 73 ml/min/leg vs. REMI & ES = 289 ± 148 ml/ min kg) or Vd (REMI = 286 ± 49 ml/kg vs REMI & ES = 248 + 40 ml/kg). A linked sigmoid Emax PK-PD model was used and the pharmacodynamic parameters were not statistically different. Mean Emax and EC50 after REMI were 18.0 ± 6.0 Hz and 32 ± 12 ng/ml; and after REMI + ES were 19 + 4.8 Hz and 26 + 8.6 ng/ml. Conclusions. At the doses tested, there is no pharmacokinetic or pharmacodynamic interaction between remifentanil and esmolol in the rat. Plenum Publishing Corporation, 1997 remifentanil nationallicence esmolol nationallicence pharmacokinetics nationallicence pharmacodynamics nationallicence electroencephalogram nationallicence Haidar Sam Pharmacokinetics-Biopharmaceutics Laboratory, USA aut Moreton J. Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 100 Penn Street, AHB 540C, 21201, Baltimore, Maryland aut Liang Zhongming Pharmacokinetics-Biopharmaceutics Laboratory, USA aut Hoke John Glaxo-Wellcome Research Institute, Research Triangle Park, Five Moore Drive, 27709, North Carolina aut Muir Keith Glaxo-Wellcome Research Institute, Research Triangle Park, Five Moore Drive, 27709, North Carolina aut Eddington Natalie Pharmacokinetics-Biopharmaceutics Laboratory, USA aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1817-1823 0724-8741 14:12<1817 1997 14 11095 https://doi.org/10.1023/A:1012156502624 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012156502624 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Haidar Sam Pharmacokinetics-Biopharmaceutics Laboratory, USA aut NATIONALLICENCE 700 1- Moreton J. Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 100 Penn Street, AHB 540C, 21201, Baltimore, Maryland aut NATIONALLICENCE 700 1- Liang Zhongming Pharmacokinetics-Biopharmaceutics Laboratory, USA aut NATIONALLICENCE 700 1- Hoke John Glaxo-Wellcome Research Institute, Research Triangle Park, Five Moore Drive, 27709, North Carolina aut NATIONALLICENCE 700 1- Muir Keith Glaxo-Wellcome Research Institute, Research Triangle Park, Five Moore Drive, 27709, North Carolina aut NATIONALLICENCE 700 1- Eddington Natalie Pharmacokinetics-Biopharmaceutics Laboratory, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1817-1823 0724-8741 14:12<1817 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer