By Milo Gibaldi, Donald Perrier

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Additional info for Pharmacokinetics, Second Edition (Drugs and the Pharmaceutical Sciences: a Series of Textbooks and Monographs)

Example text

Data from Ref. 3. SUbject 2663, dose = 10 mg{kg. ) The zero-time intercept obtained by extrapolation of the terminal linear phase to t = 0 is An' Successive application of the method of residuals (Appendix C) will yield linear segment(s) with slope(s) and intercept(s) from which the remaining value(s) of A and A can be determined. The constants A R. and AR. may be obtained graphically as shown in Fig. 4 or with the aid of a digital computer. The best approach is to fit the entire plasma concentration-time curve by means of a digital computer program which provides a nonlinear regression analysis of the curve (Appendix H).

106) For a given drug, as the absorption rate constant increases, the time required for the maximum plasma concentration to be reached decreases. The maximum plasma concentration is described by SUbstituting tmax for t in Eq , (1. 94) : C -Kt -k t k FX a O (max _ e a max) max = V(k - K) e a (1. 107) However, a simpler expression can be obtained. 108) a Substituting for e -k a t max, according to (1. 108). in (1. 110) Y The values of C ma x and t max under the special circumstance when k a = K is of mathematical interest and will be considered briefly.

Arch. Int. Pharmacodyn. 156:380 (1965) . 3. A. Goldstein. Biostatistics-An Introductory Text. Macmillan, New York, 1964. 4. G. R. Wilkinson and A. H. Beckett. Absorption, metabolism and excretion of the ephedrines in man: I. The influence of urinary pH and urine volume output. J. Pharmacol. Exp. Ther. 162:139 (1968) . 5. J. A. Taylor. Pharmacokinetics and biotransformation of chlorpropamide in man. Glin. Pharmacol. Ther. 13: 710 (1972). 6. W. H. Barr, L. M. Gerbracht, K. Letcher, M. Plaut, and N.