RT Journal Article
SR Electronic
T1 Morbid Obesity Alters Both Pharmacokinetics and Pharmacodynamics of Propofol: Dosing Recommendation for Anesthesia Induction
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1579
OP 1583
DO 10.1124/dmd.116.071605
VO 44
IS 10
A1 Dong Dong
A1 Xuemei Peng
A1 Jie Liu
A1 Hao Qian
A1 Jiayang Li
A1 Baojian Wu
YR 2016
UL http://dmd.aspetjournals.org/content/44/10/1579.abstract
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.