Hyperfiltration and Metabolism Before and After a Low‐Calorie, Pre‐Gastric Bypass Surgery Diet: Significance for Concentrations of Hydrophilic and Lipophilic Drugs

Psychotropic drug concentrations increase/decrease with hydrophilicity/lipophilicity after a low-calorie pre-bariatric surgery diet. To investigate underlying mechanisms, body weight and serum creatinine/cystatin C changes over the diet period were characterized and suggested to reflect changes in glomerular filtration and metabolic capacity, respectively. The greater the individual weight loss, the greater the concentration increase in hydrophilic drugs that undergo glomerular filtration, for example, pregabalin and gabapentin, suggesting that this reflects decreased glomerular hyperfiltration. By contrast, for highly lipophilic drugs, for example, mirtazapine and sertraline, the greater the individual creatinine and cystatin C loss, the greater the decrease in drug concentration, interpreted as increased drug metabolism based on decreased liver inflammation and steatosis. Venlafaxine/O-desmethylvenlafaxine displayed a complicated pattern suggesting the involvement of both glomerular filtration and metabolism. Serum concentrations of modestly lipophilic drugs, for example, duloxetine and (es)citalopram, were not significantly affected by the diet. In conclusion, hydrophilicity- and lipophilicity-related changes in drug concentrations over the diet period covary with markers of changes in hyperfiltration and metabolism, respectively. This implies that weight and creatinine/cystatin C changes could provide quantitative indications regarding expected drug concentration changes following fasting for hydrophilic and lipophilic drugs, respectively, which could be of value when therapeutic drug monitoring is not available.