The pharmacokinetics and electroencephalogram response of remifentanil alone and in combination with esmolol in the rat.
Pharm Res
; 14(12): 1817-23, 1997 Dec.
Article
en En
| MEDLINE
| ID: mdl-9453074
ABSTRACT
PURPOSE:
The goal of this study was to determine if the co-administration of esmolol (ES), a short acting cardioselective beta-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 +/- 15 g) were surgically implanted with stainless steel cerebrocortical EEG electrodes three days before the study. Each rat was dosed with REMI (15 micrograms/kg/min), and REMI & ES (15 micrograms/kg/min and 600 micrograms/kg/min) for 21 minutes in a random crossover design. Six serial blood samples were collected over 25 minutes into test-tubes containing 0.5 ml 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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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piperidinas
/
Propanolaminas
/
Antagonistas Adrenérgicos beta
/
Electroencefalografía
/
Analgésicos Opioides
Límite:
Animals
Idioma:
En
Revista:
Pharm Res
Año:
1997
Tipo del documento:
Article
País de afiliación:
Estados Unidos