Answer to Practice Problem #2 Dose- and Time-Dependent Pharmacokinetics Tutorial:

From the graph above you’ll note that as dose increases, the half-life increases. However, as the dose continues to increase, the curve flattens out and again does not change with dose, albeit at a longer half-life. This is because as dose increases, the capacity-limited pathway becomes saturated, increasing the half-life. As the dose continues to be increased, the fraction of the dose eliminated by the capacity-limited pathway becomes less and less, while the fraction eliminated via the first-order pathway increases. Eventually, the amount eliminated by the capacity-limited pathway becomes insignificant and the compound behaves as one eliminated via a first-order process only … though still at a higher half-life than at lower doses.
ã 2005 -
Craig K. Svensson, Pharm.D., Ph.D.
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