Excretion rate constant

Thus, the overall elimination rate constant (ke[) here is the sum of the urinary excretion rate constant (ke) and the metabolism rate constant (km) ... 

Portmann and co-workers then studied the kinetic pathways in man for hydroxynalidixic acid, the active primary metabolite.(26) The rate constants for glucuronide formation, oxidation to the dicarboxylic acid and excretion of hydroxynalidixic acid were calculated. Essentially total absorption of hydroxynalidixic acid was found in every case. Good agreement between experimental and theoretical plasma levels, based on the first order rate approximations used for the model, was found. Again, the disappearance rate constant, kdoi was found to be very similar for each subject, although the individual excretion and metabolic rate constants varied widely. The disappearance rate constant, k was defined as the sum of the excretion rate constant, kg j and the metabolic rate constants to the glucuronide and dicarboxylic acid, kM-j and kgj, respectively. 

Because kinetic rate constants are not readily available in the literature, Thomann et al. (1992) used a set of formulas to estimate the gill uptake rate constant and an excretion rate constant. The uptake rate constant is a function of the respiration rate of the organism and the efficiency of chemical transfer across the organism s membrane. The excretion rate constant is related to the uptake rate constant and Kow. 

Biota excretion rate constant k = 0.07 h-1 from whole body willow shiner (Tsuda et al. 1992) ... 

Similarly, the overall elimination rate constant can also be written as the sum of metabolic and excretion rate constants for each organ or tissue where metabolism or excretion of a drug takes place. For the previous example in Equation (10.74), where a drug that undergoes hepatic metabolism as well as renal and bile excretion, the overall rate constant becomes... 

Because TCDD is widely distributed in the environment and because it is very toxic there have been several studies of its bioconcentration using different species of fish and different experimental approaches. Values of Kb from uptake and excretion rate constants ranged from 9.27 x lO to 159 x lO, considerably less than the value derived from the data used above. The major differences were observed in values reported for ki, which varied from 108 to 2300 mL g day . This discrepancy may reflect limitations of the experimental procedures used and may also be influenced by the available concentration of TCDD. If concentrations used are higher than the reported solubility or reduced by the presence of DOM, an incorrect value for the actual concentration in solution will affect the estimate of ki. It is clear that the determination of Kb for compounds of low 5w is a significant experimental challenge. 

Figure 5.18 Relation between the excretion rate constant ( 2) and octanol-water partition coefficient (ATd,oct) for polyhalogenated hydrocarbons chlorinated dibenzofurans O, chlorinated dibenzodioxins O, brominated biphenyls T, chlorinated naphthalenes , brominated benzenes , chlorinated biphenyls , chlorinated benzenes. [Reproduced with permission from A. Opperhuizen and D. T. H. M. Sijm, Environ. Toxicol. Chem. 9, 175 (1990). Copyright SETAC, Pensacola, FL, USA.]...

The excretion rate constant (XJ is given by the percentage excreted xK ... 

Figure 3.13 Scheme and setup of onecompartment intravenous bolus model eliminated exclusively by urinary excretion. X, mass (amount) of drug in the blood/body at time t X, mass (amount) of unchanged drug in the urine at time t fC , first-order excretion rate constant. 

In Fig. 3.17, note that the intercept of the graph represents (Xu) o, which equals administered dose because of the assumption made that the drug is being completely removed in unchanged form. The slope of the graph permits the determination of the excretion rate constant,... 

Figure 3.17 A semilogarithmic plot of amount of drug remaining to be excreted against time following the administration of a drug as an intravenous bolus (Equation 3.20). K, first-order renal excretion rate constant K, elimination rate constant.

Obtain the elimination half life (ti/2) and the elimination rate constant K (which in this case equals the excretion rate constant ICu) from the graph by employing the methods described previously. 

Figure 3.18 Scheme of one-compartment intravenous bolus model of drug eliminated by both urinary excretion and metabolism. X,mass (amount) of drug in the blood/body at time, t X , mass of unchanged drug in the urine at time t Xm, mass of metabolite in the blood/body at time f X u, mass of metabolite in the urine at time t ff , first-order renal excretion rate constant (time ) K , first-order metabolite formation rate constant (time ) Kmu, first-order metabolite excretion rate constant (time ). 

The data reported in column 7 (i.e. ARE or [(A u)=o — (Au)tl) is plotted against time (data in column 6 of the table) on semilogarithmic paper (Fig. 3.21). The slope of the graph should permit the determination of the elimination rate constant and the intercept on the y-axis represents the value for (Xu) , which, in this example, is equal to the administered dose. Note that, since the drug is assumed to be totally removed in an unchanged form, the elimination rate constant is equal to the excretion rate constant, and the cumulative amount of drug excreted in the urine at time infinity, (Xu) , is equal to the administered dose. 

Figure 3.22 A typical rectilinear (a) or semilogarithmic (b) plot of rate of excretion against average time (t) following the administration of o drug os on intravenous bolus (Equations 3.25). /C , first-order renal excretion rate constant Xq, drug at time zero K, elimination rate constant.

If the rate of excretion is plotted (Fig. 3.24) against the average time, on semilogarithmic paper, the slope will permit the determination of the elimination rate constant (X) and the intercept will represent the initial rate of excretion. Please note that from the knowledge of the intercept value (mgh ) and the administered dose (mg), one can determine the excretion rate constant (XJ. 

A lower creatinine clearance value will affect other so-called "constant" parameters such as the elimination and/or excretion rate constants (K or jy, the elimination half life (ti/2) and, possibly, the apparent volume of distribution. These, in turn, will influence the value of any other pharmacokinetic parameter mathematically related to them. (This example is for a one-compartment model). These parameters include plasma concentration (Cp) at any time t, the area under the concentration versus time curve from t— 0 to t= °°, and clearance. 

Values for the elimination rate constant (X), the excretion rate constant (X ) and the metabolic rate constant (Xm) are required to calculate the amount of procainamide (unchanged form) excreted in urine at 4 h, the amount of the metabolite N-acetylprocainamide in urine... 

---