Dose rate constant

The dose rate constant ky for y radiation depends on the energy of the y rays and on the decay scheme of the radionuclide. Values of ky for various radionuclides are listed in Table 22.3. For rough estimation, it is useful to know that a point-like radiation source of 1 GBq emitting y rays with energies of 1 MeV transmits an ion dose rate of about 0.03 R h at a distance of 1 m. 

Table 22.3. Dose rate constants ky for various radionuclides (The frequency of the y transitions is taken into account).

FIG. 7.2. Dose rate constant for a monoenergetic point isotropic 7-source as a function of 7-energy. 

In addition to the elimination rate constant, the half-life (T/i) another important parameter that characterizes the time-course of chemical compounds in the body. The elimination half-life (t-1/2) is the time to reduce the concentration of a chemical in plasma to half of its original level. The relationship of half-life to the elimination rate constant is ti/2 = 0.693/ki,i and, therefore, the half-life of a chemical compound can be determined after the determination of k j from the slope of the line. The half-life can also be determined through visual inspection from the log C versus time plot (Fig. 5.40). For compounds that are eliminated through first-order kinetics, the time required for the plasma concentration to be decreased by one half is constant. It is impottant to understand that the half-life of chemicals that are eliminated by first-order kinetics is independent of dose. ... 

The dose-rate was varied by lining the irradiation chamber of the gamma cell irradiation by lead foil of uniform thickness [17]. The dose was kept constant at 0.15 and 0.35 KGy for copolymerization of AM-AANa and AM-DAEA-HCl system, respectively. The results are shown in Figs. 2 and 3, which show that the rate of polymerization, Rp increases while the degree of polymerization (DP ) and the intrinsic viscosity [17] decrease with the dose-rate. The exponents of the dose-rate for AM-AANa system [17,54] were determined to be ... 

After oral dosing, the bi-exponential Bateman function holds true with the absorption rate constant (Ka). 

A special case for reduced bioavailabilty results from first-pass extraction that sometimes might be subjected to saturable Michaelis-Menten absorption kinetics. The lower the hepatic drug clearance is (Clhep) in relation to liver blood flow (Ql), or the faster the drug absorption rate constant (Ka), and the higher the dose (D) are, the more bioavailable is the drug (F). 

In a study of pregnant rats that were exposed to radiolabeled methyl parathion by single dermal application, half-life elimination rate constants for various tissues ranged from 0.04 to 0.07 hour, highest values noted in plasma, kidneys, and fetus. Of the applied radioactivity, 14% was recovered in the urine in the first hour postapplication. By the end of the 96-hour study, 91% of the applied dose had been recovered in the urine. Fecal excretion accounted for only 3% of the administered dose (Abu-Qare et al. 2000). 

In practice, one will seek to obtain an estimate of the elimination constant kp and the plasma volume of distribution Vp by means of a single intravenous injection. These pharmacokinetic parameters are then used in the determination of the required dose D in the reservoir and the input rate constant k (i.e. the drip rate or the pump flow) in order to obtain an optimal steady state plasma concentration... 

The area under the PCP concentration-time curve (AUC) from the time of antibody administration to the last measured concentration (Cn) was determined by the trapezoidal rule. The remaining area from Cn to time infinity was calculated by dividing Cn by the terminal elimination rate constant. By using dose, AUC, and the terminal elimination rate constant, we were able to calculate the terminal elimination half-life, systemic clearance, and the volume of distribution. Renal clearance was determined from the total amount of PCP appearing in the urine, divided by AUC. Unbound clearances were calculated based on unbound concentrations of PCP. The control values are from studies performed in our laboratory on dogs administered similar radioactive doses (i.e., 2.4 to 6.5 pg of PCP) (Woodworth et al., in press). Only one of the dogs (dog C) was used in both studies. 

A is a function of the two rate constants (ka and kei), the apparent volume of distribution (Vd), and the amount of drug absorbed (Dg). After ka and kei have been evaluated and A has been determined by extrapolation, a value for Vd can be calculated if it is assumed that Dg is equal to the dose administered, i.e., absorption is 100% complete. 

The conductivity K induced by radiation absorption at dose rate I (eV°=cm-3 s-1) is given by K = uc, where c the is free ion concentration and u is the sum of mobilities of positive and negative carriers. The establishment of steady state requires equal rates of generation and recombination, or IGR /100 = kc2 where k is the second-order recombination rate constant. Eliminating c between these... 

The ratio (Q) of the estimated elimination rate constant or total body clearance relative to normal renal function is used to determine the dose or dosing interval alterations needed (CLfaii is the clearance with impaired renal function). 

These in vivo and in vitro human metabolism studies indicate that pyrethroids undergo rapid metabolism and elimination as observed in rats, and qualitative metabolic profiles (e.g., kinds of metabolites) of pyrethroids are assumed to be almost the same between humans and rats, suggesting that a large database of animal metabolism of pyrethroids could provide useful information for the evaluation of behavior of pyrethroids in humans. Nowadays, human pesticide dosing studies for regulatory propose are severely restricted in the US, and thus detailed comparison of in vitro metabolism (e.g., metabolic rate constants of pathways on a step-by-step basis) using human and animal tissues could be an appropriate method to confirm the similarity or differences in metabolism between humans and animals. 

A variety of rate constants and other parameters can be obtained from IV and oral dosing data sets, provided that good coverage of the distribution, elimination, and... 

The following data was obtained after the administration of a single 500-mg dose of a drug by slow intravenous infusion. Calculate the AUC, elimination rate constant, and the biological half-life of the drug. 

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