PT  - JOURNAL ARTICLE
AU  - Dong Dong
AU  - Xuemei Peng
AU  - Jie Liu
AU  - Hao Qian
AU  - Jiayang Li
AU  - Baojian Wu
TI  - Morbid Obesity Alters Both Pharmacokinetics and Pharmacodynamics of Propofol: Dosing Recommendation for Anesthesia Induction
AID  - 10.1124/dmd.116.071605
DP  - 2016 Oct 01
TA  - Drug Metabolism and Disposition
PG  - 1579--1583
VI  - 44
IP  - 10
4099  - http://dmd.aspetjournals.org/content/44/10/1579.short
4100  - http://dmd.aspetjournals.org/content/44/10/1579.full
SO  - Drug Metab Dispos2016 Oct 01; 44
AB  - The 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/m2) 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/m2; 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.