Download Pharmacokinetics, Second Edition (Drugs and the by Milo Gibaldi, Donald Perrier PDF

By Milo Gibaldi, Donald Perrier

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The Laplace transform of (1. 88) is sX ::: k X - KX a a (1. 89) The rate of loss of drug from the absorption site is dX ~:::-kX dt a a (1. 90) The Laplace transform of which is sX a - FX ::: -k X 0 a a (1. dministration. Solving (1. Jor Xa, substituting this value for Xa in (1. 89), and solving for X yields 34 Pharmacokinetics x = (s (1. 92) + K)(s + k ) a By employing a table of Laplace transforms, the following biexponential relationship between the amount of drug in the body and time results: _ e -k t a) (1.

14. P. J. McNamara, W. A. Colburn. and M. Gibaldi. Absorption kinetics of hydroflumethiazide. J. Clin. Pharmacol. 18:190 (1978) . 2 Multicompartment Models Most drugs entering the systemic circulation require a finite time to distribute fully throughout the available body space. This fact is particularly obvious upon rapid intravenous injection. During this distributive phase, drug concentration in the plasma will decrease more rapidly than in the postdistributive phase. Whether or not such a distributive phase is apparent depends on the frequency with which blood samples are taken.

16 Average hydroflumethiazide concentrations in plasma after a single 100 mg oral dose to 12 healthy subjects. The solid line represents the best fit of the data assuming zero-order abosrption [Eq. 125)], and the dashed line represents the best fit assuming firstorder absorption [Eq. (1. 94)]. (From Ref. 16). 42 Pharmacokinetics where kO is the apparent zero-order absorption rate constant and t is time after drug administration. During absorption, T = t. After absorption apparently ceases, T is a constant corresponding to the absorption time.

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