CYP3A4 and obesity due to melanocortin 4 receptor deficiency: For dose adjustment in patients with obesity, the following PK assumptions have been proposed: 1) the volume of distribution increases for lipophilic drugs but not for hydrophilic molecules; 2) lean body weight serves as a size descriptor and better predicts clearance and volume of distribution; 3) CYP3A4 activity is decreased, and UGTs is increased; 4) glomerular filtration rate is increased.