Impact of aminophylline on the pharmacodynamics of propofol in beagle dogs

Soo Han Lee, Hyun Ji Kang, Seok Joon Jin, Do Yang Park, Yoon Ji Choi, Byung Moon Choi, Eun Kyung Lee, Gyu Jeong Noh

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4 Scopus citations


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 AUCinf, 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: ke0 = 0.805/min, E0 = 0.76, Emax = 0.398, Ce50 na = 2.38 μg/mL (without aminophylline-exposure), Ce50 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.

Original languageEnglish
Pages (from-to)599-612
Number of pages14
JournalJournal of Pharmacokinetics and Pharmacodynamics
Issue number6
StatePublished - 9 Nov 2014

Bibliographical note

Funding Information:
We are grateful to Ae-Kyung Hwang, B.S. (technician), Hyun-Jeong Park, B.S. (technician), and A-rum Kim, B.S. (technician) from the Clinical Research Center of Asan Medical Center (Seoul, Korea) for measuring plasma concentrations of propofol. This work was supported by the Student Research Grant (12-13) of University of Ulsan College of Medicine and Grant No. 2010-301 from the Asan Institute for Life Sciences, Seoul, Korea.

Publisher Copyright:
© 2014, Springer Science+Business Media New York.


  • Aminophylline
  • Interaction
  • Pharmacodynamics
  • Pharmacokinetics
  • Propofol


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