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Lecture-08 Pharmacokinetics III

Lecture-08 Pharmacokinetics III - Time to steady state...

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Time to steady state concentration Once again assume a drug follows first-order kinetics and is administered by continuous iv administration. The C ss depends on the rates of administration and elimination of the drug. However, the rate of approach to the steady state concentration only depends on the elimination rate constant (assuming first-order kinetics). This is known as the plateau principle .

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Attained fraction of steady state According to the plateau principle any fraction of the C ss depends only on k t. and thus the time required to reach a particular fraction depends only on the elimination rate constant k . The time to reach a fraction of C ss , is called the fractional attainment and is described by the equation f = 1-e -kt Remember that k = 0.693 / t 1/2 For any drug, the time to plateau is roughly 5 half- lives. eg. f = 1 - e =~ 1
Dosing regimens for repeated i.v. administration If a drug is given intermittently rather than continuously, it is impossible to maintain a single C ss . Rather, the concentration will fluctuate around an average C ss . Maintenance doses (D m ) are administered following each maintenance interval (T m ) such that the average rate of drug intake equals D m / T m . Remember that Q = C ss x Cl. Therefore, Average C ss = (D m / T m ) / Cl and thus, D m = Cl x T m x average C ss , or D m = k V x T m x average C ss

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How does one choose maintenance doses and intervals? What’s the advantage of low Dm and Tm? Changes in C ss over time are smaller, therefore safer. What’s the advantage of higher Dm and Tm? Less frequent drug administration leads to better patient compliance. The maintenance dose keeps the blood concentration between the minimum therapeutically-effective concentration ( C ther ) and the toxic concentration ( C tox ) such that Dm = (C tox - C ther ) x V The loading dose would be L = V x C tox
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