Plasma concentration versus time plots

In the total plasma response approach, the bioavailability of a compound is determined by measuring its plasma concentration at different times (up to weeks) after single or long-term ingestion of the compound from supplements or food sources. Generally, a plasma concentration-versus-time plot is generated, from which is determined the area-under-curve (AUC) value used as an indicator of the absorption of the componnd. Here, the term relative bioavailability is more appropriate since AUC valnes of two or more treatments are usually compared. This is in contrast to absolnte bioavailability for which the AUC value of the orally administered componnd is compared to that obtained with intravenous administration taken as a reference (100% absorption). 

A typical semi-log plasma concentration versus time plot is shown in Fig. 4. This figure shows that pharmacokinetic data can also be expressed in terms of a half-life, called the biological half-life, which bears the same relationship to kei as that shown in Eqs. (14) and (15). 

Once a semilog plasma concentration versus time plot begins to follow simple first-order elimination kinetics, the remaining AUC can be calculated in one step using Eq. (45). 

Figure 1.3 A typical plasma concentration versus time plot (rectilinear paper) following the administration of a dose of a drug by an intravascular route.

In colurim 1 of the table, the time values are recorded that correspond to the observed plasma concentrations. This is done only for the absorption phase. In colurim 2, the observed plasma concentration values provided only from the absorption phase are recorded (i.e. all values prior to reaching maximum or highest plasma concentration value). In column 3, the plasma concentration values obtained only from the extrapolated portion of the plasma concentration versus time plot are recorded (these values are read from the plasma concentration-time plot) and, in column 4, the differences in the plasma concentrations (Cp)diff between the extrapolated and observed values for each time in the absorption phase are recorded. 

For example, in Eq. 11.12 (for intravenous bolus), (Cp)o represents the intercept of the plasma concentration versus time profile following the administration of a single dose of a drug. In Eq. 12.13 (for extravascularly administered dose), we can obtain the intercept value from the plasma concentration versus time plot. In both Eqs 11.12 and 12.13, the denominator term is identical (i.e. 1 - For an intravenous bolus, maximum or peak plasma concentration occurs at time 0 and, for an extravascular route, maximum concentration will occur at peak time (Fig. 12.3). 

A and B are the two empirical constants (i.e. y-axis intercepts) of the plasma concentration versus time plot, and a and jS are the two rate constants associated with the two phases of the concentration versus time plot. 

Figure 13.13 is the plasma concentration versus time plot from which the slow disposition rate constant and the empirical constant B can be obtained. 

Normally, the plasma concentration is used as a measure of the amount of drug in the body, and a plot of plasma concentration versus time has the same characteristics as the plot in Fig. 1. A semilogarithmic... 

Fig. 4 Semilogarithmic plot of plasma concentration versus time for a drug administered by rapid intravenous injection.

For drugs that are both metabolized and excreted unchanged, semilogarithmic plots of plasma concentrations versus time will provide values of kei. 

Thus after 6 hours the semilog plot of Cp versus time shown in Fig. 10 becomes a straight line and kei can be determined from the slope. Therefore, the overall elimination rate constant for a drug may be accurately determined from the tail of a semilog plot of plasma concentration versus time following extravascular administration if ka is at least five times larger than kei. 

It is not necessary to apply the trapezoidal rule to the entire plasma concentration versus time curve in order to calculate the total AUC. After the semilog plot becomes a straight line, the remaining area out to t = can be calculated using the following equation ... 

Fig. 14 Plot of plasma concentration versus time showing accumulation following multiple intravenous injections. 

The AUC is determined by plotting the plasma concentration versus time on normal rectilinear graph paper, dividing the area up into trapezoids, and calculating the area of each trapezoid (Fig. 3.24). The total area is then the sum of the individual areas. Although the curve theoretically will never meet the x axis, the area from the last plasma level point to infinity may be determined from Ct/ke. The units are mgL 1hr. 

The first step in performing PK modeling is to graph the plasma concentration versus time profile to examine the shape of the curve and to get some preliminary ideas whether the data would fit a one-, two- or a three-compartment PK model. From the semi-logarithmic plot (Figure 1), it was obvious that the compound exhibited either two- or three-compartment kinetics. 

Fig. 9. Semilogarithmic plots of plasma concentrations versus time for 3 doses of salicylate administered to the same subject, illustrating capacity-limited elimination. At low plasma concentrations, parallel straight lines are obtained from which the first-order elimination rate constant can be estimated. As long as concentrations remain sufficiently high to saturate the process, elimination follows zero-order kinetics (C. A. M. van Ginneken et al., J. Pharmacokinet. Biopharm., 1974,2, 395-415).

Half-life can be readily determined from a plot of log plasma concentration versus time and was for many years considered to be the most important characteristic of a drug. Early studies examining drug disposition in disease states were compromised, by a reliance on half-life as a sole measure of disposition changes. It is now appreciated that half-life is a secondary, derived parameter that relates to and depends on the primary parameters of clearance (CL) and volume of distribution (E) according to the following relationship in Eq. (25) ... 

Time to peak = time from administration to Cmax-Figure 1-1-3. Plot of Plasma Concentration Versus Time... 

What shape would you expect for a plot of measured plasma concentrations versus time for each of the standard PK models What shape would you expect for a plot of In(C ) versus time for each of the standard PK models ... 

Pharmacokinetic Analysis. Standard noncompartmental analyses were conducted to assess ATI and ATF pharmacokinetics using WinNonlin software (v. 2.1) (Pharsight, Mountain View, CA). The areas under the plasma concentration versus time curve from time zero to inhnity (AUCint) were determined via the log-linear trapezoidal method. The terminal half-life was determined from the relationship of ti/2 = In 2/, where k is the negative slope of the terminal phase of the InC versus time plot. Systemic clearance (CL) was estimated by dividing the administered dose by AUCint. The volume of distribution at steady state (Vss) was determined by the product of clearance and the mean residence time. 

In relation to drug residues, a pharmacokinetic property of major significance is the very late terminal elimination half-life (see Sections 2.3.1 and 2.7.1). For many drug classes, a semi-logarithmic plot of plasma concentration versus time, after intravenous dosing, reveals a... 

Figure 1.4 A typical plot (rectilinear paper) of plasma concentration versus time following the (oral) administration of an identical dose of a drug via identical dosage form but different formulations. MTC, minimum toxic concentration MEC, minimum effective concentration.

The elimination half life of a dmg may be determined by employing Eq. 3.12, provided that the value of the elimination rate constant is known or provided. Alternatively, the elimination half life may be obtained from the semilogarithmic plot of plasma concentration versus time data, as described in Fig. 3.10. 

Second, from the semilogarithmic plot of plasma concentration versus time, -K = (slope) x 2.303, so... 

We plotted plasma concentration versus time data on a two-cycle semilogarithmic graph paper and then determined the following ... 

In this question, plasma concentration versus time data is provided following the administration of two different doses of a drug (cinoxacin Cinobac). Because of the assumption of the first-order process and passive diffusion, one would expect the plasma concentration of a drug at any time to be directly proportional to the dose administered however, the fundamental pharmacokinetic parameters of a dmg will remain unaffected by the administered dose. We plotted... 

In this problem, in addition to determining the pharmacokinetic parameters such as the elimination half life, elimination rate constant and the apparent volume of distribution of the drug, the systemic clearance of the drug and the area under the plasma concentration time curve for the administered dose of the drug are required. The plot of plasma concentration versus time data was made on suitable semilogarithmic paper. From the graph, the following can be determined (for healthy subjects) ... 

This question involves two different doses of an identical drug (promethazine) in an identical dosage form (tablet), via an identical route of administration (oral) of an identical formulation (made by the same manufacturer). Plasma concentration versus time data were plotted on suitable semilogarithmic graph paper. As mentioned above, greater variation can occur in the values in parts a-d because of the technique employed. This variation, in turn, will be reflected in the answers for the peak time, peak plasma concentration and the intercept of the plasma concentration versus time profile. 

How would you compare this plot with the plot of the area under the plasma concentration versus time curve [(AUC)o against the administered dose following the administration of a... 

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