Concentration-time profiles for

The concentration-time profile for this system was calculated for a particular set of constants k = 1.00X 10 6 s k = 2.00X 10 4 molL 1,and [A]0 = 1.00xl0 3M. The concentration-time profile, obtained by the numerical integration technique explained in Section 5.6, is shown in Fig. 2-11. Consistent with the model, the variation of [A] is nearly linear (i.e., zeroth-order) in the early stages and exponential near the end. 

A new chapter (5) on reaction intermediates develops a number of methods for trapping them and characterizing their reactivity. The use of kinetic probes is also presented. The same chapter presents the Runge-Kutta and Gear methods for simulating concentration-time profiles for complex reaction schemes. Numerical methods now assume greater importance, since useful computer programs are available. The treatment of pH profiles in Chapter 6 is much more detailed. 

Figure 3, Concentration-time profiles for reactants and selected products in the...

Also, if conversion of drug to active metabolite shows significant departure from linear pharmacokinetics, it is possible that small differences in the rate of absorption of the parent drug (even within the 80-125% range for log transformed data) could result in clinically significant differences in the concentration/ time profiles for the active metabolite. When reliable data indicate that this situation may exist, a requirement of quantification of active metabolites in a bioequivalency study would seem to be fully justified. 

To illustrate the subtle differences between the iso-pH and gradient-pH methods, ketoprofen was used in a series of simulation calculations. Figure 3.5a shows the concentration-time profiles for ketoprofen under an iso-pH condition. Consider the case of iso-pH 3, where the molecule is essentially uncharged in solution (pKa... 

Figure 2 Simulated in vitro drug-release profiles (panels a and b) and resultant plasma concentration—time profiles for a drug with a 1—hr half-life (panel c) and a 6—hr half-life (panel d).

Figure 5 Predicted concentration-time profiles for the three...

The predicted concentration-time profiles for all three formulations are shown in Figure 5 (panel a). These simulations use the fitted in vitro profiles for input to the model. For comparison, the simulations assuming zero order release are shown in panel b. Although the zero order simulations may be useful for initial specification of target profiles, they offer little of value for selecting specific formulations for the in vivo study or for study design (e.g., selection of sampling times),... 

Figure 10 Mean observed concentration-time profiles for the three extended-release formulations, fast ( ), medium (o), and slow ( ), whose in vitro dissolution data are shown in Figure 3 (panel a) and the derived mean absorption-time profiles (panel b).

Figure 13 Comparison of the mean observed and predicted concentration-time profiles for the three ER formulations, fast ( ), medium (o), and slow ( ), whose dissolution behavior is shown in Figure 3. Pharmacokinetic parameters F= 1, ka = 1000 hr-1, io = 0.17hr 1, V = 114L, fcoi =, coi = 9hr, abs = 96hr. Dosing parameters dose = 10 mg, r = 24hr. IVIVC equation xViVO=Jcvitro (1 1 IVIVC panel a) or 4th order polynomial shown in Figure 11 (panel b). Double Weibull (drug release) parameters for each of the three formulations are listed in Table 2.

Pharmacokinetic Model for Simulation of Concentration-Time Profiles for Orally Administered Extended-Release Dosage Forms... 

FIGURE 2 3 Typical concentration-time profiles for irradiation of a propylene-NO, mixture in a smog chamber. Reprinted with permission from Niki et ai. 

The blood concentration-time profile for a theoretical drug given extravascularly (e.g., orally) is shown in Figure 5.2. Some pharmacokinetic parameters, such as Cmax, T x> area under the curve, and half-life, can be estimated by visual inspection or computation from a con-... 

Concentration-time profile for a hypothetical drug administered intravenously. Following intravenous dosing of a drug, blood concentrations of the drug reach a maximum almost immediately. Y-axis is logarithmic scale. 

Concentration-time profile for a hypothetical drug administered extravascularly. C ,ax, maximum concentration achieved. T ax. time required to achieve maximum concentration. AUC = Area under the curve. Y-axis is on logarithmic scale. 

Concentration-time profile for a hypothetical drug administered orally in multiple doses. The drug is administered once every half-life (i.e., every 8 hours). Drug continues to accumulate (i.e., concentrations rise) until steady state (rate in = rate out) is reached at approximately 5 half-lives (about 40 hours). 

Figure 16.7 shows some typical concentration-time profiles for irradiation of a propene-NO mixture in the evacuable chamber of Fig. 16.3. The loss of the reactants, and the formation of the most commonly monitored secondary pollutants 03, PAN, and the oxygenates HCHO and CH3CHO are shown (Pitts et al., 1975).

Figure 16.13, for example, shows the concentration-time profiles for a run in the evacuable chamber shown in Fig. 16.3 and for one in the evacuable chamber of Akimoto et al. (1985). The calculation, which assumes no radical source, curve A, clearly underpredicts Oa by a large margin. However, inclusion of a photoenhanced production of HONO via reaction (14), curve B, matches the observations quite well (Sakamaki and Akimoto, 1988). 

FIGURE 16.18 Concentration-time profiles for 03, NO., NMHC, H202, HCHO, and higher aldehydes (RCHO) predicted using four different chemical submodels two carbon bond four models (CB4.1 and CB4-TNO), a RADM model (RADM2), and the EMEP model (adapted from Kuhn et al., 1998). 

FIGURE 16.22 Observed ( ) and model-predicted concentration-time profiles for 03 at three locations in southern California... 

Figure 3.25 Log10 plasma concentration time profile for a foreign compound after intravenous administration. The plasma half-life (fo) and the elimination rate constant (fce ) of the compound can be determined from the graph as shown.

Keinath, T. M. Weber, W. J., Jr. "A Mathematical Model for Prediction of Concentration-Time Profiles for Design of Fluid-Bed Adsorbers," Tech. Publ., Res. Project No. WP-00706, Fed. Water Poll. Control Admin., U.S. Dept, of Interior, April 1968. 

The simplest reactions have the one-step unimolecular or bimolecular mechanisms illustrated in Table 4.1 along with their differential rate equations, i.e. the relationships between instantaneous reaction rates and concentrations of reactants. That simple unimolecular reactions are first order, and bimolecular ones second order, we take as self-evident. The integrated rate equations, which describe the concentration-time profiles for reactants, are also given in Table 4.1. In such simple reactions, the order of the reaction coincides with the molecularity and the stoichiometric coefficient. 

Fig. 4.3 Concentration-time profiles for two parallel first-order unidirectional reactions of a single compound A.

It is often useful to determine how much of the drug actually penetrates the membrane barrier (e.g., skin or gastrointestinal tract) and gets into the blood stream. This is usually determined experimentally for oral and dermal routes of administration. The area under the curve (AUC) of the concentration-time profiles for oral or dermal routes is compared with the AUC for IV routes of administration. The AUC is determined by breaking the curve up into a series of trapezoids and summing all of the areas with the aid of an appropriate computer program (Figure 6.5). 

Figure 6.5 Plasma concentration time profile for oral exposure to a toxicant and depiction of AUCs determined by summation of trapezoids at several time periods.

Figure 4.10 Chamber concentration/time profiles for four kinds of dry building materials At the beginning of the test, a dose of formaldehyde was injected into the chamber air, the measurement stopped when the chamber formaldehyde concentration hardly changed (Zhang et al., 2007a).

Fig. 3.16 Convex-upward terminal concentration-time profile for a mAb with two elimination pathways, one linear and one non-linear route.

Fig. 13.2 Mean concentration-time profiles for tasidotin after single-dose administration for patients enrolled in Study 103.

Fig. 13.5 Mean concentration—time profiles for ILX651-C-carboxylate after single-dose tasidotin administration in patients enrolled in Study 103.

The plasma concentration/time profile for the 4 mg intravenous dose exhibited an initial rapid fall over 1-2 h followed by a slower decline over 30 h. The experimental data were fitted to a biexponential rate equation to give the following mean parameter values ... 

Figure 5.20 shows concentration-time profiles for the decomposition of hydrocortisone butyrate at 60°C in a buffered aqueous propylene glycol (50 w/w%, pH 7.6). Consecutive, irreversible, first-order kinetic models [i.e., Equation (5.119a), Equation (5.119b), and Equation (5.119c)] fit reasonably well with the experimental... 

Figure 13-16. Plasma concentration-time profile for a child with ADHD after an oral administration of 17.5 mg of racemic MPH. The plasma concentrations were determined using a validated method described elsewhere. Reprinted with permission from [58].

Figure 13-20. Mean plasma concentration-time profile for patients subsequent to a daily oral administration of Gleevec or STI571 (free base) for 28 consecutive days (steady-state). The sampling period was up to 48hr post-dose. The dose regimen was escalated from 25 to 600mg/day until a favorable hematologic response was observed. Reprinted with permission from [60].

Figure 1 Plasma concentration time profiles for a single 42-mg dose of a hypothetical drug with a half-life of 8 hours, Vj 42 liters, and oral bioavailability of 80%. Dashed curve intravenous bolus dose. Solid curve oral dose. Dotted horizontal lines represent plasma concentrations required for efficacy (green) and for the onset of adverse events (red).

Figure 2 Plasma concentration time profiles for the drug in Fig. 1 displayed with a logarithmic scale for plasma concentration. Dashed curve intravenous dose. Solid curve oral dose. The half-life may be calculated from the slope. Note that the concentration values first must be converted to the natural logarithms. T 12 = 0.693 / [(In 100 - In 12) / 24 hour] = 8 hours.

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