Absorption rate constant and

Other applications of the previously described optimization techniques are beginning to appear regularly in the pharmaceutical literature. A literature search in Chemical Abstracts on process optimization in pharmaceuticals yielded 17 articles in the 1990-1993 time-frame. An additional 18 articles were found between 1985 and 1990 for the same narrow subject. This simple literature search indicates a resurgence in the use of optimization techniques in the pharmaceutical industry. In addition, these same techniques have been applied not only to the physical properties of a tablet formulation, but also to the biological properties and the in-vivo performance of the product [30,31]. In addition to the usual tablet properties the authors studied the following pharmacokinetic parameters (a) time of the peak plasma concentration, (b) lag time, (c) absorption rate constant, and (d) elimination rate constant. The graphs in Fig. 15 show that for the drug hydrochlorothiazide, the time of the plasma peak and the absorption rate constant could, indeed, be... 

Fig. 15 Computer plots for (a) absorption rate constant and (b) time of plasma peak. (From Ref. 31.)... 

H Yuasa, T Iga, M Hanano, J Watanabe. Relationship between in vivo first-order intestinal absorption rate constant and the membrane permeability clearance. J Pharm Sci 78 922-924, 1989. 

Of all the absorption models tested, the last absorption model (Lrst-order model where the absorption rate constant and lag time were treated as a mixture model) Ltted the data best. In 97% of the subjects, the population-estimated absorption rate constant was-1 vfifttia lag time of 0.821 h, and in the remaining 3% of the subjects, the population-estimated absorption rate constant was 0.361 h1 without a lag time (Bonate et al., 2004). 

Figure 1. Four-level molecular model. QiS is the collisional-transfer rate constant from level i to level j, TV is the sum of the electronic quenching and spontaneous emission rate constants, W,t is the absorption rate constant, and Wlt is the stimulated emission rate constant. WIt and WtI are proportional to the laser power PL. The dashed vertical line separates levels le and 2e, which are treated as an isolated system, from those levels not affected directly by the laser radiation.

To describe the relationship between colonic absorption rate constants and the lipophilicity of xenobiotics, the hyperbolic equation proposed by Wagner applies [2]. 

Below or at the CMC In the experiments with synthetic surfactants at CMC, the best fit describing the relationship between absorption rate constant and lipophilicity corresponds to a potential equation [26] ... 

This equation is for an intravenous dose. For drugs given by mouth, the equation must be modified as shown previously for estimating the dose from the time and and would need knowledge of the absorption rate constant and the bioavailabil-ity(F . 

Both between-subject and interoccasion variances were estimated on clearance of nelfinavir, absorption rate constant, and clearance of M8. The residual error with a proportional error model was modeled for nelfinavir and M8 separately. The effect of ritonavir was found to have a statistically significant impact on the clearance of M8 but not on that of nelfinavir. The apparent clearance of M8 was 3.23 L/h it decreased to 1.87 L/h when nelfinavir was coadministered with ritonavir. After univariate selection, a large number of covariates were included in the full model. According to the acceptance criteria, none of the effect on clearance of nelfinavir on... 

FIGURE 1.1 The three most commonly used pharmacokinetic models in explaining the pharmacokinetic behavior of drugs. The symbols C, P, S, and D represent central, peripheral, shallow, and deep compartments, whereas the first-order rate constants, symbolized by k j, represent drug transport from compartment i to compartment j. ka, and kd represent a bolus rV dose, the absorption rate constant, and constant rate infusion, respectively. 

The absorption rate constant and the absorption phase half life are obtained from the residual or feathering method. From the data in Fig. 6.20, the differences between the observed and the extrapolated plasma concentrations are calculated (Table 6.6, column 4) and are then plotted against time (column 1) on semilogarithmic paper. 

Is it accurate to state that the larger the difference between the intercept of the plasma concentration time data and the peak plasma concentration, the larger is the difference between the absorption rate constant and the elimination rate constant Please consider. 

The following approach will permit determination of the absorption rate constant and peak time. As shown above, only at peak time does the rate of absorption equal the rate of elimination Ka Xa)max = KX ax-... 

In patients with renal impairment, the elimination half life of procainamide is reported to be 14 h (range, 9-43 h). When a 250 mg procainamide tablet is administered to a renally impaired subject, the absorption rate constant and the elimination rate constant are reported to be 2.8 h and 0.0495 h , respectively. However, the intercept of the plasma concentration-time profile is observed to be 1.556 pgmL . ... 

---