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Drug distribution transport rates

The distribution transport rate (r is ) is a measure of how quickly drug molecules are exchanged between the plasma and the tissues. A rapid distribution transport rate causes the plasma and tissues to come quickly into equilibrium with each other, whereas a slower rate will cause a prolonged approach to equilibrium. As with the rate of absorption, different types of PK modeling approaches can be employed to approximate distribution rates. In the case of distribution there are essentially two types of models, instantaneous distribution and first-order distribution. The difference between the two types of models is in the number of compartments used to represent the drug disposition in the body. [Pg.214]

As in all standard two-compartment models, the rate of drug distribution transport between the two compartments is taken to follow first-order or linear kinetics. [Pg.240]

The rate of drug distribution transport between the central compartment (containing the systemic circulation) and any tissue compartment is taken to follow first-order or linear kinetics. This means that the rate of drug transport from compartment 1 to any other compartment is proportional to the amount of drug in compartment 1. Similarly, the rate of drug transport... [Pg.260]

Because the amounts and density of these transporters vary along the gastrointestinal tract, it is necessary to introduce a correction factor for the varying transport rates in the different luminal and enterocyte compartments. Due to the lack of experimental data for the regional distribution, and Michaelis-Menten constants for each drug in Table 18.2, we fitted an intrinsic (concentration-independent) transport rate for each drug to closely approximate the experimental %HIA. This... [Pg.435]

Figure 13.1. Compartmental model based on clearance and volume (Section 13.2.4.1). The drug is administered at a rate Ri into the central compartment, which is characterized by a volume of distribution K. The drug is transported to and from the peripheral compartment with inter-compartmental clearance CL12 and CL21, respectively (usually it is assumed that there is no net transport between the two compartments if the concentrations in both compartments are equal in this case CL21 = CLi2)- The peripheral compartment is characterized by a volume of distribution 1 2-Elimination may take place from both compartments and is characterized by clearance CL o and CL20, respectively. Figure 13.1. Compartmental model based on clearance and volume (Section 13.2.4.1). The drug is administered at a rate Ri into the central compartment, which is characterized by a volume of distribution K. The drug is transported to and from the peripheral compartment with inter-compartmental clearance CL12 and CL21, respectively (usually it is assumed that there is no net transport between the two compartments if the concentrations in both compartments are equal in this case CL21 = CLi2)- The peripheral compartment is characterized by a volume of distribution 1 2-Elimination may take place from both compartments and is characterized by clearance CL o and CL20, respectively.
Figure 13.2. Compartmental model based on rate constants (Section 13.2.4.1). The drug is administered at a rate into the central compartment, which is characterized by a volume of distribution V. The drug is transported to and from the peripheral compartment with rate constants and feii, respectively. Figure 13.2. Compartmental model based on rate constants (Section 13.2.4.1). The drug is administered at a rate into the central compartment, which is characterized by a volume of distribution V. The drug is transported to and from the peripheral compartment with rate constants and feii, respectively.
PK modeling can take the form of relatively simple models that treat the body as one or two compartments. The compartments have no precise physiologic meaning but provide sites into which a chemical can be distributed and from which a chemical can be excreted. Transport rates into (absorption and redistribution) and out of (excretion) these compartments can simulate the buildup of chemical concentration, achievement of a steady state (uptake and elimination rates are balanced), and washout of a chemical from tissues. The one- and two-compartment models typically use first-order linear rate constants for chemical disposition. That means that such processes as absorption, hepatic metabolism, and renal excretion are assumed to be directly related to chemical concentration without the possibility of saturation. Such models constitute the classical approach to PK analysis of therapeutic drugs (Dvorchik and Vesell 1976) and have also been used in selected cases for environmental chemicals (such as hydrazine, dioxins and methyl mercury) (Stem 1997 Lorber and Phillips 2002). As described below, these models can be used to relate biomonitoring results to exposure dose under some circumstances. [Pg.190]

Since the target site of a drug is rarely at the site of administration or in the systemic circulation, delivery of the drug to the target tissue by the distribution process is often a critical determinant of the drug s effectiveness. Many of the physiochemical and physiological factors involved in the distribution process have been discussed previously in Section 10.2 or in Chapter 7. This section will focus on the means by which the distribution process is incorporated and represented in PK models. This involves mathematical terms to represent both the extent of distribution and the rate of distribution transport. [Pg.213]

These time zero values can be substituted into Equation (10.231) and combined with Equation (10.202) to show that F = Fi at time zero. Another common distribution volume term is defined for the time when distributional steady-state occurs, as illustrated in Eigure 10.14. There is no net transport of drug between compartments 1 and 2 at steady-state, as the transport rates in each direction are exactly equal. At the time when this occurs, a steady-state distribution volume (F i) can be defined by the equation... [Pg.246]


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