Multicompartmental

Fig. 1.1 Multicompartmental model world, schematic overview. Dashed arrows denote sinks, solid arrows exchange processes.

The three dimensional multicompartmental chemistry transport model MPI-MCTM [Lammel et al (2001), Semeena and Lammel (2003), Gughelmo (2008)] was run for 40 years with a resolution of T21L19 in the atmosphere and GR30L40 in the ocean. The ocean biogeochemistry started from spin-up fields and the atmosphere from an initial run, necessitating a physical spin-up of 2 years prior to the actual simulation. Within a mn of 40 years the model produces its own climate based... 

In the cladoceran Daphnia magna, about 90% of the total body lead burden is adsorbed to the exoskeleton (Berglind et al. 1985). In animals with a vertebral column, total amounts of lead tend to increase with age. By far the most lead is bound to the skeleton, especially in areas of active bone formation (Barth et al. 1973 Tsuchiya 1979 USEPA 1980 Hejtmancik et al. 1982 Mykkanen etal. 1982 Peter and Strunc 1983 De Michele 1984 Eisler 1984 Berglind etal. 1985 Marcus 1985). The retention of lead stored in bone pools poses a number of difficulties for the usual multicompartmental loss-rate models. Some lead in bones of high medullary content, such as the... 

A form of multicompartmental modelling in which all compartments are linked in a linear chain with each compartment connecting only to its immediate neighbour. 

A form of multicompartmental modelling in which there is a central compartment to which a stated number of peripheral compartments are connected. 

S. Muller, A. Hutson, V. Arya, G. Hochhaus, Assessment of Complex Peptide Degradation Pathways via Structured Multicompartmental Modeling Approaches The Metabolism of Dynorphin Al-13 and Related Fragments in Human Plasma , J. Pharm. Sci. 1999, 88, 938-944 S. Muller, G. Hochhaus, Metabolism of Dynorphin A 1-13 in Human Blood and Plasma , Pharm. Res. 1995, 12, 1165- 1170. 

H. Ringsdorf, P. Lehmann, R. Weberskirch, Multicompartmentation—a concept for the molecular architecture of life, 217th ACS National Meeting, Anaheim (CA), 1999. 

E.M. Landau and J.J. DiStefano III, Multiexponential, multicompartmental and noncompartmental modeling II, Data analysis and statistical considerations, Am. J. Physiol. 246 (1984) R665-R677. 

Therefore, the pharmacokinetic parameters, which can be derived from blood level measurements, are important aids to the interpretation of data from toxicological dose-response studies. The plasma level profile for a drug or other foreign compound is therefore a composite picture of the disposition of the compound, being the result of various dynamic processes. The processes of disposition can be considered in terms of "compartments." Thus, absorption of the foreign compound into the central compartment will be followed by distribution, possibly into one or more peripheral compartments, and removal from the central compartment by excretion and possibly metabolism (Fig. 3.23). A very simple situation might only consist of one, central compartment. Alternatively, there may be many compartments. For such multicompartmental analysis and more details of pharmacokinetics and toxicokinetics, see references in the section "Bibliography." The central compartment may be, but is not necessarily, identical with the blood. It is really the compartment with which the compound is in rapid equilibrium. The distribution to peripheral compartments is reversible, whereas the removal from the central compartment by metabolism and excretion is irreversible. 

For a further discussion of multicompartmental analysis, which is beyond the scope of this book, the reader is referred to the section "Bibliography."... 

Muller, S., A. Hutson,V. Arya, and G. Hochhaus. 1999. Assessment of complex peptide degradation pathways via structured multicompartmental modeling approaches the metabolism of dynorphin Al-13 and related fragments in human plasma [In Process Citation]. 

Absorption of a drug into the theoretical central or main compartment may be followed by distribution into one or more peripheral compartments, or the drug may undergo excretion or metabolism from the central compartment. While compartmental analysis of drug distribution can be informative, it is beyond the scope of this book. For more details on the effect of multicompartmental distribution of a drug on pharmacokinetics, see references in the Bibliography. 

Minekus, M., Marteau, P., Havenaar, R., and Huis in t Veld, J. H. J. (1995). A multicompartmental dynamic computer-controlled model simulating the stomach and small intestine. Altern. Lab. Anim. 23, 197-209. 

Recent PBPK models have tried to address benzene metabolism in an effort to derive animal-to-human extrapolations (Bois et al. 1991a Medinsky 1995 Medinsky et al. 1989a Spear et al. 1991 Travis et al. 1990). Each model described a multicompartmental model that attempted to relate the generation of metabolites to end points of benzene toxicity. The generation of hydroquinone and muconaldehyde in the liver, with further metabolism in the bone marrow, has been addressed as well as the available data allow. However, the model is not sufficiently refined to allow it to accurately predict human metabolism. Thus, although PBPK modelling has provided a means to improve animal to human extrapolations, the models need to be improved. 

Sontag (1986) Pharmacokinetic Model. An extended multicompartmental model (see Figure 2-9) describing the kinetic behavior of uranium (absorption, distribution, and excretion as a function of time) in the organs of male and female rats was developed using data taken from experiments performed on 13-month-old male and female Sprague-Dawley rats intravenously injected with 1.54 mCi/kg (57 kBq/kg) U-uranyl citrate and sacrificed at 7, 28, 84, 168, or 336 days after injection. 

PHYSIOLOGICAL BASIS OF MULTICOMPARTMENTAL MODELS OF DRUG DISTRIBUTION... 

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