How does obesity affect residence time dispersion and the shape of drug disposition curves? Thiopental as an example.
The effect of obesity on the shape of drug disposition curves was explained using the residence time concept without assuming well-mixed compartments. The mean (MDRT) and relative dispersion (RD2(D)) of disposition residence time of drug were predicted as function of percentage body fat by lumping the organs into fat and nonfat tissues, utilizing the fact that MDRT and RD2(D) act as a scale and shape parameter of disposition curves, respectively. The longer sojourn time of lipophilic drugs in adipose tissue leads to an increase in RD2(D) when the fraction of body fat increases. This explains the change in the shape of disposition curves observed in obese patients, where the increase in MDRT is accompanied by a proportionately great prolongation of the terminal half life. The model also predicts a decrease in whole body distribution clearance with increasing residence time dispersion (RD2(D)).
Weiss
Michael
M
Department of Pharmacology, Martin Luther University, Halle, Germany. michael.weiss@medizin.uni-halle.de
D050154:Adiposity / Q000502:physiology; D000818:Animals; D004285:Dogs; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics*; D015233:Models, Statistical; D009765:Obesity / Q000378:metabolism*; D010599:Pharmacokinetics; D051381:Rats; D013874:Thiopental / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D006993:Hypnotics and Sedatives; D013874:Thiopental