Effect of Vd change on pharmacokinetic parameters

With the interactive graph provided in the previous post you can vary the body weight by using the slider. Here, simplistically, the body weight directly changes the volume of distribution, so effectively the slider just changes the Vd.

What you will observe is that as you change the body weight, the half-life changes, and correspondingly, the time to reach steady state. The accumulation index also changes, because it is affected by the ratio of half-life/dose interval. The AUC and steady state concentrations remain unchanged because these are affected by Clearance and not Vd. The peaks and troughs changes, and these may affect the efficacy-toxicity balance of the dosage regimen if either efficacy or toxicity is affected by peaks or troughs.

In the display above, the body weight was altered from 70kg to 140kg. The half-life and time to reach steady state both corresponding doubled. While the AUC remained unchanged, the peaks have been lowered while the trough has increased. Whether the dosage regimen needs to be adjusted will depend on the therapeutic ratio of the drug, and the therapeutic objectives.