title: Impact of aminophylline on the pharmacodynamics of propofol in beagle dogs.
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.
authors.affiliation: Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Korea.
authors.forename: Soo-Han
authors.initials: SH
authors.lastname: Lee
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Kang
authors.forename: Seok-Joon
authors.initials: SJ
authors.lastname: Jin
authors.forename: Do-Yang
authors.initials: DY
authors.lastname: Park
authors.forename: Yoon-Ji
authors.initials: YJ
authors.lastname: Choi
authors.forename: Byung-Moon
authors.initials: BM
authors.lastname: Choi
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Lee
authors.forename: Gyu-Jeong
authors.initials: GJ
authors.lastname: Noh
mesh_terms: D000465:Algorithms; D000628:Aminophylline / Q000008:administration & dosage*; D000818:Animals; D019540:Area Under Curve; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D008297:Male; D008954:Models, Biological; D015742:Propofol / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000628:Aminophylline; D015742:Propofol