General concentration-time curves

Given the postulated reaction scheme, the net rate of reaction often takes a simple form when it is expressed in terms of the concentration of the intermediate. Such an expression is algebraically correct, and is the form one needs so as to propose and interpret the mechanism. This form is, however, usually not useful for the analysis of the concentration-time curves. In such an expression the reaction rate is given in terms of the concentration of the intermediate, which is generally unknown at the outset. To eliminate the concentration term for the intermediate, one may enlist certain approximations, such as the steady-state approximation. This particular method is applicable when the intermediate remains at trace levels. 

Figure 3.11 shows the general characteristics of the concentration-time curves for the three components A decreases exponentially, R rises to a maximum and then falls, and S rises continuously, the greatest rate of increase of S occurring where R is a maximum. In particular, this figure shows that one can evaluate k and k2 by noting the maximum concentration of intermediate and the time when this maximum is reached. Chapter 8 covers series reactions in more detail. 

For these reactions the concentration-time curves are of little generality for they are dependent on the concentration of reactant in the feed. As with reactions in parallel, a rise in reactant concentration favors the higher-order reaction a lower concentration favors the lower-order reaction. This causes a shift in and this property can be used to improve the product distribution. 

Since the area under the plasma concentration-time curve (AUC) for a drug is a measure of the total amount of a drug reaching the general circulatory system, the bioavailability of a drug may also be defined in terms of the AUC as ... 

Weiss, M., Generalizations in linear pharmacokinetics using properties of certain classes of residence time distributions. II. Log-concave concentration-time curves following oral administration, Journal of Pharmacokinetics and Biopharmaceutics, Vol. 15, No. 1, 1987, pp. 57-74. 

Area under the plasma/seruin/blood concentration-time curve from time zero to time t (AUCO-z), where t is the last sampling time point with a measurable concentration of the API in the individual formulation tested. The method of calculating AUC-values should be specified. In general AUC should be calculated using the linear/log trapezoidal integration method. The exclusive use of compartmental-based parameters is not recommended. 

The relationship between bioavailability and area under the plasma concentration-time curve is nonlinear and absorption rate dependent when the plasma protein binding of a drug is concentration dependent. Two drug products from which a drug is equally well absorbed will produce different values for the area under the plasma concentration-time curve if a difference exists in the absorption rate. Generally, such a comparison will overestimate the extent of drug absorption of the more slowly absorbed product. 

Generally, the efficacy and the safety of a drug depend on the area under the plasma concentration—time curve (AUC), and CLtot is the determining factor of the AUC as shown by Eq. (6.4) ... 

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