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Lecture-8

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Since an immediate effect is desired, a loading dose (L) of the drug is rapidly administered to fill body stores and establish C ther . At steady state the amount of drug in the body is VC ss = L Example: Assume we are about to give a drug to a 70 kg man and that for this drug C ther = 2 mg/L, t 1/2 = 80 min, and his body is 70% water. What is k? 0.693 / 80 = 0.0087 min -1 What is V? 0.7 L/kg x 70 kg = 49 L What is Q? Q = k VC ss = 0.0087 min -1 x 49 L x 2 mg/L = 0.85 mg/min What is Cl? Cl = k V = 0.0087 min -1 x 49 L = 0.43 L/min What is L? L = VC ss = 49 L x 2 mg/L = 98 mg

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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 .
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

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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
How does one choose maintenance doses and intervals?

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