• Dong Dong, Xuemei Peng, Jie Liu, Hao Qian, Jiayang Li, and Baojian Wu.
• Ocular Surface Research Center and Institute of Ophthalmology, School of Medicine, Jinan University, Guangzhou, China (D.D.); Department of Anesthesiology, First Affiliated Hospital of Jinan University, Guangzhou, China (X.P., J.Li); Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, China (H.Q., B.W.); and Department of Pharmacy, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (J.Liu).
• Drug Metab. Dispos. 2016 Oct 1; 44 (10): 1579-83.

AbstractThe prevalence of obesity has markedly increased worldwide. Obese patients pose significant challenges to anesthesiologists with regard to accurate dosing of anesthetics due to potentially altered pharmacokinetics (PK). Here we determined the PK and pharmacodynamics (PD) of propofol for anesthesia induction in morbidly obese (MO) subjects (body mass index >35 kg/m(2)) at two dosing regimens: dosing based on total body weight and lean body weight (LBW), respectively. The propofol pharmacokinetic profile was well fitted with a two-compartment model. Both elimination clearance (223%-243% of controls, who had a body mass index <25 kg/m(2); P < 0.01) and peripheral compartment volume (156%-180% of controls; P < 0.01) were significantly increased in MO subjects, resulting in an equal or decreased propofol level in plasma (total body weight-based dosing). Furthermore, propofol PD (measured by the bispectral index) was adequately described by a PK/PD model that linked an effect compartment to the two-compartment PK model through a sigmoidal Emax model. All PD parameters except EC50 values (the half maximal effect concentration) were similar (P > 0.05) between MO subjects and controls. Morbid obesity led to a significant decrease (37.9%-38.6%; P < 0.01) in EC50 values, which suggests increased brain sensitivity to propofol in the MO population. Moreover, dose reduction (i.e., dosing based on LBW) generated identical anesthetic effects in MO subjects compared with controls. In conclusion, morbid obesity significantly altered both PK and PD of propofol. LBW was a better weight-based dosing scalar for anesthesia induction with propofol in MO subjects.Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

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