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Showing posts with label Vd. Show all posts
Showing posts with label Vd. Show all posts

Tuesday, April 4, 2017

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.

Sunday, August 21, 2016

Visualizing the effects of body weight and clearance on the plasma concentration - time profile

Here is an interactive graph that helps you visualize how the volume of distribution (simplistically affected here by the body weight) and the clearance of a drug affect the plasma concentration - time profile of a drug that is orally administered 3 times a day (8 hourly).

Play around with the sliders provided and see how the profile changes. Note how the half-life changes as well as how the steady state plasma concentrations, area under the curve (AUC), minimum and maximum concentrations change. How about the time required to reach steady state? And how much accumulation occurs under the different situations?

Think about how individual profiles may vary because of differences in body weights and the ability of their bodies to clear specific drugs.


Concentration vs Time
[No canvas support]

BW(kgs): 70       

Clearance: 9.1

Dose Interval = 8hrs,

Accumulation Index: 2.0       Halflife: 8.0