Transit compartment

In most other cases, the lysosomes are a transit compartment en route to the cytoplasm. In case the targeted agent is lysosomally unstable (e.g. DNA) this compartment should be avoided. 

Sun.Y.N. and W.J. Jusko. 1998. Transit compartments versus gamma distribution function to model signal transduction processes in pharmacodynamics. 

The transit compartment model (Figure 18.4B) is an extension of the tanks-in-series model in which one (or more) of the signaling compartments incorporates nonlinearity via a Hill exponent h (138). The equations are given by... 

We have developed a model called the dispersion model (Figure 18.5) and compared it to the tanks-in-series and transit compartment models (139). The parameters of the dispersion model estimate the relative roles of diffusion, convection, and chemical reaction in signal transduction. We found that the dispersion model was capable of simultaneously fitting mRNA and protein dynamics for tyrosine aminotransferase (TAT) after methylprednisolone treatment from a published PD study quite well (140). 

Finally, the compartments for red blood cells are initialized. The first compartment is set to the ratio of the rate of red blood cells being formed over a fixed normalized value. Because the other compartments are transit compartments, they are assnmed to have the same initial conditions at steady state. 

E. D. Lobo and J. P. Balthasar, Pharmacodynamic modeling of chemotherapeutic effects application of a transit compartment model to characterize methotrexate effects in vitro. Am Assoc Pharm Sci Pharm Sci 4(4) 42 (2002). 

Transit Compartment Models for Signal Transduction Processes... 

FIGURE 23.7 Schematic of a time-dependent transduction model with three transit compartments (Mi) characterized by a mean transit time (t). The production of the drug-receptor complex RC) initiates the PD cascade and a linear transducer function E and Eq. (23.20)) may be substituted for RC in the absence of specific receptor dynamics. 

Implementation of the general signal transduction model requires a search for an optimal number of transit compartments (N), which usually is the fewest that... 

Once formed, RC translocates into the cell nucleus (RC(N)) and this process is modeled using a transit compartment reflecting signal transduction ... 

Another approach to modeling lag-times is to model the kinetic system using differential equations with the lag-time manifested through a series of intermediate or transit compartments between the absorption compartment and observation compartment (Fig. 8.1). For example, the differential equations for Model A in the figure would be written as... 

It should be noted that 1/lag is sometimes referred to as ktr, the transit rate constant. Such a series of differential equations does not have an all-or-none outcome and is more physiologically plausible. Using a differential equation approach to model lag-compartments the rise in concentration to the maximal concentration is more gradual. But, as the number of intermediate lag-compartments increase so does the sharpness in the rate of rise so that an infinite number of transit compartments would appear as an all-or-none function similar to the explicit function approach (Fig. 8.2). Also, as the number of intermediate compartments increase the peakedness around the maximal concentration increases. 

Figure 8.2 Concentration-time profiles illustrating the difference between modeling lag-time using an explicit function [Eq. (8.33)] versus a differential equation approach [Eq. (8.34)] with a variable number of intermediate transit compartments. Concentrations were simulated using a 1-compartment model having a dose of 100 mg, V = 125 L, ka = 0.7 per hour, kio = 0.15 per hour and a lag-time of 3 h. The explicit function models lag-times as all-or-none, whereas the differential equation approach models lag-times more gradually.

Savic, R., Jonker, D.M., Kerbusch, T., and Karlsson, M.O. Evaluation of a transit compartment model versus lag-time model for describing drug absorption delay. Presented at the Population Analysis Group Europe, Uppsala, Sweden, 2004. 

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