Animal models tissue distribution

Absorption, Distribution, Metabolism, and Excretion. Levels of cresols in blood were obtained from a single case report of a dermally exposed human (Green 1975). Data on the toxicokinetics of cresols in animals were contained in two acute oral studies that provided only limited quantitative information on the absorption, metabolism, and excretion of cresols (Bray et al. 1950 Williams 1938). A more complete oral toxicokinetics study, in addition to studies using dermal and inhalation exposure, would provide data that could be used to develop predictive pharmacokinetic models for cresols. Inclusion of several dose levels and exposure durations in these studies would provide a more complete picture of the toxicokinetics of cresols and allow a more accurate route by route comparison, because it would allow detection of saturation effects. Studies of the tissue distribution of cresols in the body might help identify possible target organs. 

No toxicokinetic studies have been performed on humans. Thus, the appropriateness of animals as models of white phosphorus toxicokinetics in humans is unknown. A similar tissue distribution of orally administered radiolabeled white phosphorus was observed in rats, rabbits, and mice. It seems reasonable to expect that tissue distribution in humans would be similar. No other multiple species studies were located. 

This chapter has described the pharmacokinetics of PT 2 -MOE partially modified ASO following parenteral administration, and has shown that ASOs in this chemical class distribute extensively to many tissue types, with prolonged half-lives. Moreover, exposure-response relationships have been established in both animal models and humans. However, there are a few tissues to which parenter-ally administered oligonucleotides do not distribute, or are distributed minimally these include brain, muscle, eyes, and skin. Consequently, ASOs targeted to these tissues will require local delivery, as outlined in Chapter 10. 

Animal models have shown that formulations and delivery routes can be used to alter the tissue distribution of ASOs. By making use of the knowledge gained through these studies, ASOs may be delivered selectively to a variety of target tissues including some that would otherwise not be easily accessible, such as in the... 

PBPK models for 2,3,7,8-TCDD are discussed below. The pharmacokinetic behavior of 2,3,7,8-TCDD, especially distribution, has been shown to be dose-dependent and involves protein binding and enzyme induction in hepatic tissue. Thus, terms describing these interactions have been included in the animal models described below. Furthermore, since induction of these dioxin-binding proteins is a process mediated by the interaction of a dioxin-receptor (the Ah receptor) complex with specific binding sites on DNA additional terms were included in the models. For a detailed explanation regarding the Ah receptor and its involvement in the mechanism of action of 2,3,7,8-TCDD and structurally related halogenated aromatic hydrocarbons, see Section 2.4.2. 

Another important characteristic of photoreactive agents is their apparent affinity for certain targets that are of special interest for interventional vascular therapists, As most photosensitizers fluoresce, the kinetics of their distribution in vascular tissue can be investigated both at macroscopic and microscopic levels using fluorescence imaging techniques (Fig, 3), Numerous studies on porphyrin, chlorin, texaphryin, pheophorbide and phthalocyanine photosensitizers in various animal models have documented selective localization in... 

A suitable animal model can be used for in vivo pharmacokinetic assessment of a topically applied elastic liposome formulation. Rats and mice are most common but tend to provide an over-estimate compared to human skin as the skin is more permeable. Piglets provide a closer approximation to human skin permeability and have been used for some evaluations of elastic liposomes (9, 34). Appropriate animal ethics committee approval is required. A generalised protocol is outlined in the following section but there can be considerable variation depending on the complexity of information sought, i.e., if the determination of distribution into tissues is required in addition to absorption into the circulation ... 

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