ISSN:
1573-904X
Keywords:
remifentanil
;
esmolol
;
pharmacokinetics
;
pharmacodynamics
;
electroencephalogram
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1012156502624
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