Species differences in absorption

Although there appears to be no significant species differences in absorption rates for small lipophilic drugs, some interspecies differences are noted with water-soluble drugs absorbed from distal airspaces of in vivo mammalian lungs [112], These species differences have not been systematically studied yet. However, some marked differences were reported for protein absorption rates... 

List two reasons for species differences in absorption of a chemical. 

Species differences in absorption may occur for any of the following reasons differences in gastrointestinal pH or anatomy, differences in rate of blood flow to the absorption site, differences in breathing rate, differences in skin type, and the presence or absence of fur. 

Renwick (1989) notes species differences in gastric pH, ranging from 1.9 in rabbits to between 3.8 and 5.0 in rats. Such differences in gut environments may affect species differences in absorption rate of white phosphorus or its inorganic breakdown products, although quantitative comparisons between species were not located. 

In Section III, emphasis was placed on flux kinetics across the cultured monolayer-filter support system where the passage of hydrophilic molecular species differing in molecular size and charge by the paracellular route was transmonolayer-controlled. In this situation, the mass transport barriers of the ABLs on the donor and receiver sides of the Transwell inserts were inconsequential, as evidenced by the lack of stirring effects on the flux kinetics. In this present section, the objective is to give quantitative insights into the permeability of the ABL as a function of hydrodynamic conditions imposed by stirring. The objective is accomplished with selected corticosteroid permeants which have been useful in rat intestinal absorption studies to demonstrate the interplay of membrane and ABL diffusional kinetics (Ho et al., 1977 Komiya et al., 1980). 

Sex-Related Differences in Rodents. Not only are there differences in absorption, distribution, biotransformation and metabolism between species, there may also be differences between sexes within a species. Griffin et al. (1997), for example, has demonstrated sex-related differences in the metabolism of 2,4-dichlorophenoxyace-tic acid (Table 18.8). They noted that while there were differences between sexes,... 

Thome, L., and G. P. Hanson. Species differences in rates of vegetal ozone absorption. Environ. PoUut. 3 303-312, 1972. 

Species differences in the metabolism of di(2-ethylhexyl) phthalate have been reported and attempts have been made to explain the susceptibility of animals to di(2-ethylhexyl) phthalate-induced hepatic peroxisome proliferation based on their metabolic profiles (Doull et al., 1999). As mentioned above, the bulk of a di(2-ethylhexyl) phthalate dose is absorbed as the mono-ester, mono(2-ethylhexyl) phthalate, and following absorption this metabolite is subjected to extensive oxidative metabolism mediated by cytochrome P450 enzymes (Albro Lavenhar, 1989 Astill, 1989 Huber et al., 1996 Doull et al., 1999). The metabolism of mono(2-ethylhexyl) phthalate has been summarized by Doull et al. (1999) as follows (see Figure 1) ... 

Significant species differences have been observed in the absorption and disposition of di(2-ethylhexyl) phthalate. The peroxisome-proliferating effect of di(2-ethyl-hexyl) phthalate has been related most specifically in susceptible species to metabolites VI, IX and mono(2-ethylhexyl) phthalate however, analysis of the disposition data does not provide an explanation for the observed species differences in di(2-ethylhexyl) phthalate-induced hepatic peroxisome proliferation. 

Absorption. Absorption of foreign compounds from various sites is dependent on the physiological and physical conditions at these sites. These, of course, may be subject to species variations. Absorption of compounds through the skin shows considerable species variation. Table 5.2 gives an example of this and shows the species differences in toxicity of an organophosphorus compound absorbed percutaneously. Human skin is generally less permeable to chemicals than that of rabbits, mice, and rats, although there is variation. For some compounds, rat skin has similar permeability to human skin and seems to be less permeable than that of the rabbit. 

One other in situ technique can be used to determine fractional acidity in atmospheric aerosols by means of Fourier transform infrared (FTIR) spectroscopy (46). Originally, impactor samples were collected and were pressed into a KBr matrix, and then the IR spectrum was taken by attenuated total reflectance (ATR) FTIR spectroscopy to determine relative acidity, based on differences in absorption bands for sulfate and bisulfate species. Aerosols with [H+]/[S042 ] ratios greater than 1 could also be qualitatively identified. More recent innovations in the FTIR technique (47, 48) have made possible... 

Roovers and Bywater 76 examined the temperature dependents of the electronic spectrum of poly(isoprenyi)iithium and were able to calculate an equilibrium constant for the dissociation event. On the basis that the process involved was tetramers dimers, the dissociation enthalpy was determined to be 12.3 kcal/mole in n-octane while a value of 9.0 kcal/mole was found in benzene solution. The latter value was thought to be due to weak solvations of the active centers by benzene. The approach used by Roovers and Bywater 76) is predicated on the assumption that the 272 and 320 nm absorptions represent species differing in their association state. 

Ultraviolet-vis spectroscopy depends on differences in absorption intensities of species in differing protonation states using the relation... 

The absorption, distribution, metabolism, and excretion in the species used in the toxicology studies should be discussed. Quantitative or notable qualitative differences in ADME between the various animal species and humans should be discussed, as well as any references to observed species differences in toxicity and extrapolation of the findings to humans. The significance of these findings to the interpretation of the results of the carcinogenicity, bioassay, and other preclinical toxicity studies should be considered. 

The greater the depth of understanding of toxicity and agent deposition in animals and humans, the less is the uncertainty that attends extrapolation across species and routes of exposure. When such pharmacokinetic studies are done, apparent species differences in susceptibility are often found to result from differences in absorption, fate, or elimination of the potential toxic agent rather than to biological differences in susceptibility (Renwick 1993). 

Sato, K., K. Sugibayashi and Y. Morimoto (1991). Species differences in percutaneous absorption of nicorandU, J. Pharm. Scl, 80, 104-107. 

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