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Impact of aminophylline on the pharmacodynamics of propofol in beagle dogs

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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 E max model, respectively. Pharmacodynamic parameter estimates of propofol were: k e0 = 0.805/min, E 0 = 0.76, E max  = 0.398, Ce 50 na  = 2.38 μg/mL (without aminophylline-exposure), Ce 50 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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Korea

    Soo-Han Lee

  2. Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap 2-dong, Songpa-Gu, Seoul, 138-736, Korea

    Do-Yang Park & Gyu-Jeong Noh

  3. University of Ulsan College of Medicine, Seoul, Korea

    Hyun-Ji Kang

  4. Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Seok-Joon Jin, Byung-Moon Choi & Gyu-Jeong Noh

  5. Department of Anesthesiology and Pain Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea

    Yoon-Ji Choi

  6. Department of Statistics, Ewha Womans University, Seoul, Korea

    Eun-Kyung Lee

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  1. Soo-Han Lee
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Correspondence to Gyu-Jeong Noh.

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S-H. Lee and H-J. Kang contributed equally to this work.

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Lee, SH., Kang, HJ., Jin, SJ. et al. Impact of aminophylline on the pharmacodynamics of propofol in beagle dogs. J Pharmacokinet Pharmacodyn 41, 599–612 (2014). https://doi.org/10.1007/s10928-014-9377-x

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