Pharmacokinetics absorption rate constant

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... 

The pharmacokinetics of nalidixic and hydroxy-nalidixic acids have been studied by several different groups. Takasugi ejt al studied in-situ and in-vitro absorption of nalidixic acid from the gastrointestinal tracts of rats as a function of pH. They reported that the absorption of non-ionized nalidixic acid was faster than the ionized form, with the maximum absorption rate constant found when the drug was administered from a pH=3 buffer solution. The absorption in-sltu was found to be ten times the rate in-vitro, but this was dependent on several factors.(13)... 

Fig. 2.6 Effect of variation in absorption rate on plasma drug concentration. The graph shows simulated plasma concentration-time curves for theophyUine after oral administration, illustrating a 20% difference in Cpmax values resulting from variation in the absorption rate constant. Absorption rate constants top curve 2.2 per h (Cpmax 20 pg/mL) middle curve 1.0 per h (Cptnax 18 M-g/mL) bottom curve 0.7 per h. Note that tmax also changes. The established therapeutic concentration of theophyUin is 10-20 pg/mL. The most rapidly absorbed formulation produces the highest concentration and greatest chance of side effects. Also, the duration for which the plasma concentration is within the therapeutic range also varies. Pharmacokinetic parameters dose, 400 mg bioavaUabiUty, 0.8 volume of distribution, 29 L half-Ufe, 5.5 h.

For a number of years, computers have been successfully utilized in pharmacokinetics to 1) fit blood-level data to the appropriate model (single, two, or multiple compartments) and to calculate model parameters, such as absorption rate constant, elimination rate constant, half-life, and volume of distribution 2) evaluate... 

A patient taking warfarin and who had taken a decoction of S. miltiorrhiza presented with a prolonged bleeding time and melena (12) and other cases have been reported (13). Pharmacodynamic and pharmacokinetic studies in rats have shown that danshen increases the absorption rate constant, AUC, and half-lives of both R- and 5-warfarin, and reduces their clearances and apparent volumes of distribution (14,15). 

Even though the absorption rate constant (kf) defines the rate of absorption, its accurate determination is largely dependent on the adequacy of the plasma concentration-time data associated with the absorption phase of the drug. When a drug is administered orally, as a conventional (immediate-release) dosage form, or injected intramuscularly as an aqueous parenteral solution, the absorption and disposition kinetics can often be analysed in terms of a one-compartment pharmacokinetic model with apparent first-order absorption. The plasma concentration-time curve is described by the equation... 

A new molecular entity exhibiting one-compartment pharmacokinetics with first-order absorption was assumed. The typical (mean) values of the population PK parameters for the NME were 1 h 17.5L/h, and SOL for absorption rate constant (Ka), apparent clearance (CLIP), and apparent volume of distribution (V/F), respectively. An intersubject variability of 45% (coefficient of variation) was assumed for each of these parameters, and this was assumed to be lognormally distributed with a mean of zero. A proportional error model was assumed for the residual error of 15%. 

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. 

Affinity data, like substrate or receptor binding constants, rate constants, like association/dissociation, and Michealis Menten constants, inhibition constants, especially Kj and IC50 values of different enzymes, pharmacokinetic parameters, like absorption rate constants, distribution parameters, clearance, rate constants of metabolic degradation, and elimination rate constants,... 

We remain cognizant that this edition of the textbook includes some references that may be considered by some viewers not to be the most current. We, however, believe that the chosen references are classic ones best suited to illustrate a particular point. Additionally, we fully recognize that this edition omits topics such as the Wagner and Nelson method for the determination of the absorption rate constant, urinary data analysis following the administration of a drug by an extravascular route, two-compartment model pharmacokinetics for an extravascularly administered dmg, and metabolite kinetics. 

In 6 healthy subjects, oral salbutamol 4 mg four times daily for 2 weeks had no elTect on the pharmacokinetics of a single 400-mg oral dose of sulfamethoxazole (in co-trimoxazole), although the absorption rate constant was reduced by about 40% and the extent of absorption over 72 hours was increased by 22.6%. A possible reason for these effects is that salbutamol stimulates the beta receptors in the gut, causing relaxation, which allows an increased contact time, and therefore increased absorption of sulfamethoxazole. The clinical significance of this interaction is unknown, but it... 

Naproxen. A double-blind, crossover study failed to find any clinically important changes in mood or attention in healthy subjects given naproxen and diazepam." A single-dose study in 10 healthy subjects found that peak serum concentrations of naproxen 500 mg were reduced by 23%, the time to peak concentration was increased (1.36 to 2 hours) and the absorption rate constant was decreased (4.07 to 2.42 h ) by diazepam 10 mg. Other pharmacokinetic parameters were not affected. No special precautions appear to be necessary. 

Single-dose pharmacokinetics including relationship among dose and plasma concentration, absorption rate, total, metabolic and renal clearance, volume of distribution, elimination rate constant and half-life... 

Pharmacokinetics According to product label, analysis of data from a study in healthy men and women who received intravenous and subcutaneous Neumega revealed that following subcutaneous administration absorption is the rate-limiting step. Hence the elimination rate constants... 

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