Impact of aminophylline on the pharmacodynamics of propofol in beagle dogs.
J Pharmacokinet Pharmacodyn
; 41(6): 599-612, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-25150710
ABSTRACT
This study aimed to characterize pharmacodynamic interaction between propofol and aminophylline. Nine beagle dogs were randomly allocated at the propofol rates of 0.75 (group A), 1.00 (group B), and 1.25 (group C) mg/kg/min. During period 1, propofol only was infused, while during period 2, aminophylline only, at the rate of 0.69 (group A), 1.37 (group B), and 2.62 (group C) mg/kg/h. During periods 3-5, the two drugs were co-administered. The aminophylline infusion rate was 0.69 (period 3), 1.37 (period 4), and 2.62 (period 5) mg/kg/h. The aminophylline was infused from 0 to 30 h, and the propofol was infused at 24 h for 20 min. Blood samples and electroencephalograms were obtained at preset intervals. In the linear regression between log-transformed doses of aminophylline and AUC inf, the slope was 0.6976 (95% CI 0.5242-0.8710). Pharmacokinetics of aminophylline was best described by a one-compartment, with enzyme auto-induction, model. Pharmacokinetics and pharmacodynamics of propofol were best described by a three-compartment model and a sigmoid Emax model, respectively. Pharmacodynamic parameter estimates of propofol were k(e0) = 0.805/min, E0 = 0.76, Emax = 0.398, Ce(50 na) = 2.38 µg/mL (without aminophylline-exposure), C(e50 wa) = 4.49 µg/mL (with aminophylline-exposure), and γ = 2.21. Propofol becomes less potent when exposed to aminophylline. Pharmacodynamic antagonistic interaction of aminophylline with propofol sedation, may occur, not in a dose-dependent manner, but in an all-or-none response.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Propofol
/
Aminofilina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article