Accessible pool parameters

The relationships among the accessible pool parameters in the noncompartmental model are given in the following equations ... 

In these formulas C(0) is the concentration of drug in the system at time zero C(0) is the first derivative of C(0 evaluated at time zero and C is the steady-state value for the concentration of drug in the accessible pool following a constant infusion into that pool. The remaining single accessible pool parameters kg, Vtot, and MR-Tg can be calculated for either method of input using Equations 8.5 8.6, and 8.9. 

The pharmacokinetic parameters descriptive of the accessible pool are as follows (these definitions apply... 

FIGURE 8.1 (A) A system in which an accessible pool (AP) is available for test input (bold arrow) and sampling (dashed line with bullet). Loss of material from the system is indicated by the arrow leaving the system box. Material exchanging betw een the accessible pool and the rest of the system is indicated by the small arrows leaving and entering the accessible pool. The pharmacokinetic parameters estimated from kmetic data characterize the accessible pool and the system in which the accessible pool is embedded. (B) A system in which there are two accessible pools, one that is available for test input (bold arrow) and a second that is available for sampling (dashed line with bullet)-, the test input is transported to the second accessible pool as indicated by the transfer arrow. Other transfer arrows are as explained in (A). 

The pharmacokinetic parameters descriptive of the system are as follows (although these definitions apply to both noncompartmental and compartmental models, some modification will be needed for two accessible pool models as well as compartmental models) ... 

The two accessible pool model accommodates a more complex experimental format than does the single pool model. For example/ one could have inputs into both poolS/ and samples from both as well. However/ in most pharmacokinetic studies with the two accessible pool model/ pool 2 is plasma and input is only into pool 1. In this situation/ the pharmacokinetic parameters depend on bioavailability and can only be estimated up to a proportionality constant/ as is the case with so-called oral clearance (CLjF), referred to as relative clearance in this chapter. 

The kinetic parameters of the noncompartmental model are those defined previously for the accessible pool and system. However/ the formulas depend upon the experimental protocol/ especially on the mode of drug administration. In this chapter/ only the canonical inputs will be considered/ such as an intravenous bolus (or multiple boluses) or constant infusion (or multiple constant infusions). References will be given for those interested in more complex protocols. 

The following parameters can be calculated from data following a bolus injection into the first accessible pool. Let CL 2 and V[2, respectively/ be the clearance from and volume of the second accessible pool/ and let CL 2/ relf and V 2, relf be the relative clearance from and volume of the second accessible pool. Then... 

What is the advantage of using sums of exponentials to describe pharmacokinetic data in the situation of the single accessible pool model following a bolus injection or constant infusion The reason is that the integrals required to estimate the pharmacokinetic parameters are very easy to calculate ... 

This discussion will rely heavily on the following sources. First, the publications of DiStefano and Landaw (22, 23) deal with issues related to compartmental versus single accessible pool noncompartmental models. Second, Cobelli and Toffolo (3) discuss the two accessible pool noncompartmental model. Finally, Coveil et al. (4) provide the theory to demonstrate the link between noncompartmental and compartmental models in estimating the pharmacokinetic parameters. 

As discussed, the noncompartmental model divides the system into two components an accessible pool and nonaccessible pools. The kinetics of the nonacces-sible pools are lumped into the recirculation-exchange arrows. From this, as has been discussed, we can estimate pharmacokinetic parameters describing the accessible pool and system. 

Intravenous Drug Disposition. The estimation of primary pharmacokinetic parameters using noncompartmental analysis is based on statistical moment theory [45, 46]. The relationships dehned by this theory are valid under the assumption that the system is linear and time-invariant. For simplicity, we further assume that drug is irreversibly removed only from a single accessible pool (e.g., plasma space). Regardless of the route of administration, the temporal profile of plasma drug concentrations, Cp(t), can represent a statistical distribution curve. As such, the zeroth and first statistical moments (Mo and Mi) are defined as ... 

Cobelli, C., and Saccomani, M. P. (1992). Accessible pool and system parameters Assumptions and models. JPEN, J. Parenter. Enteral Nutr. 15, 45S-50S. 

The instrumental aspects of EPR have been summarized elsewhere, " although the text by Poole is especially noted for instrumental details and parameters. Obviously, to perform ENDOR experiments, one must have an EPR spectrometer, of which Bruker Biospin is the sole viable vendor at present (http //www.bruker-biospm.com/brukerepr/index.html accessed 03/01/2007). ENDOR accessories include the rf synthesizer and amplifiers and a microwave resonant cavity that includes rf cods in addition to the normal structure with field modulation coils. Locally constructed ENDOR spectrometers were more common in the past, with that of the late Clyde A. Hutchison Jr being a notable example, particularly for single-crystal studies. Such spectrometers still exist the author is familiar with those at Northwestern University. ... 

The System Supervisor must provide the Job Controller with information about the program, including the computational host ID, the number and names of all the input and output files used by the program, and the names of the libraries or pools called by the program. The Job Controller will also have access to all the information necessary to operate the scientist/user s accounts on each computational host. Using the information obtained from the System Supervisor, the Job Controller will be able to decide which job commands are necessary to attach specified input and/or output files and to attach specified software libraries. The Job Controller will also be able to choose host parameters that are machine specific. 

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