Comparison of observed and predicted first-pass metabolism of nortriptyline in humans

The extent of first-pass metabolism of nortriptyline, calculated by comparing the areas under the plasma concentration-time curves following intravenous and oral dosing in six individuals, varied from 41 to 54%. Theoretically predicted values ranged from 41 to 61% based on a plasma flow model, indicating that the clearance takes place mainly from the plasma, which does not represent the whole blood concentration.