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The Pharmacokinetics and Electroencephalogram Response of Remifentanil Alone and in Combination with Esmolol in the Rat

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Abstract

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.

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Authors and Affiliations

  1. Pharmacokinetics-Biopharmaceutics Laboratory, USA

    Sam H. Haidar, Zhongming Liang & Natalie D. Eddington

  2. Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 100 Penn Street, AHB 540C, Baltimore, Maryland, 21201

    Sam H. Haidar, J. Edward Moreton, Zhongming Liang & Natalie D. Eddington

  3. Glaxo-Wellcome Research Institute, Research Triangle Park, Five Moore Drive, North Carolina, 27709

    John R Hoke & Keith T. Muir

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  1. Sam H. Haidar
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  2. J. Edward Moreton
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  3. Zhongming Liang
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  4. John R Hoke
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  5. Keith T. Muir
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  6. Natalie D. Eddington
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Correspondence to Natalie D. Eddington.

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Haidar, S.H., Moreton, J.E., Liang, Z. et al. The Pharmacokinetics and Electroencephalogram Response of Remifentanil Alone and in Combination with Esmolol in the Rat. Pharm Res 14, 1817–1823 (1997). https://doi.org/10.1023/A:1012156502624

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  • DOI: https://doi.org/10.1023/A:1012156502624

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