Drug absorption in vivo

Table 5.1 Some factors that affect nasal drug absorption in vivo [2],...

During the last decade several in vitro models using excised mucosal segments and monolayers of epithelial cells have been established, providing an opportunity to predict nasal drug absorption in vivo while avoiding problems associated with more complex whole animals [8],... 

Figure 6.5 Relationship between drug absorption in vivo and airspace to perfusate transfer in the isolated perfused lung [142].

Kajii, H., et al. 1985. Fluorescence study on the interaction of salicylate with rat small intestinal epithelial cells Possible mechanism for the promoting effects of salicylate on drug absorption in vivo. Life Sci 37 523. 

The characteristics of membrane permeation are partition, including affinity, location, specific interaction with certain phospholipids, and diffusion kinetics. Because of the complex events involved during drug absorption in vivo, true membrane permeability modeling cannot always be expected. Therefore, many attempts have been made to develop suitable in vitro systems to study the permeation process and its dependence on membrane composition and drag physicochemical properties. 

Hanisch, G., M. Kjerling, A. Palsson, B. Abrahamsson, and A.-L. Ungell. 1999. Effects of vehicles for sparingly soluble compounds on the drug absorption in vivo. Abstract from conference Elderly people medicines, Stockholm conference center Alvsjo, 11-13 October. 

Shirasaka Y, Masaoka Y, Kataoka M, Sakuma S, Yamashita S (2008) Scaling of in vitro membrane permeabihty to predict P-glycoprotein-mediated drug absorption in vivo Drug Metab Dispos 36 916 922. 

Avdeef, A., Nielsen, P. E., Tsinman, O. PAM PA - a drug absorption in vitro model. 11. Matching the in vivo unstirred water layer thickness by individual-well stirring in microtitre plates. Eur. J. 

The use of vesicle cell membranes, isolated cells, and cell monolayers and intestinal tissue studies has provided valuable correlations with in situ and in vivo drug absorption in animals as well as correlations with drug absorption in clinical studies. Most prominent among the literature sources establishing correlations between in vitro tissue and cellular systems with drug absorption in humans are the work of Dowty and Dietsch [73], Lennernas et al. [74], and Stewart et al. [75],... 

H Lennernas, O Ahrenstedt, R Hallgren, L Knutson, M Ryde, LK Paalzow. Regional jejunal perfusion, a new in vivo approach to study oral drug absorption in man. Pharm Res 9 1243-1251, 1992. 

Raab, Y., Gerdin, B., Hallgren, R., Regional rectal perfusion a new in vivo approach to study rectal drug absorption in man, Pharm. Res. 1995, 12, 426-432. 

Fricker, G., Miller, D. S., Relevance of multidrug resistance proteins for intestinal drug absorption in vitro and in vivo, Pharmacol. Toxicol. 2002, 90, 5-13. 

Reduction of particle size increases the total specific surface area exposed to the solvent, allowing a greater number of particles to dissolve more rapidly. Furthermore, smaller particles have a small diffusion boundary layer, allowing faster transport of dissolved material from the particle surface [58]. These effects become extremely important when dealing with poorly water-soluble drugs, where dissolution is the rate-limiting step in absorption. There are numerous examples where reduction of particle size in such drugs leads to a faster dissolution rate [59-61], In some cases, these in vitro results have been shown to correlate with improved absorption in vivo [62-64]. 

It is still challenging to isolate hydrodynamic influences on drug dissolution in vivo from other factors that can play a role in absorption. 

Lennernas H, Ahrenstedt O, Hallgren R, Knutson L, Ryde M and Paalzow LK (1992) Regional Jejunal Perfusion, a New In vivo Approach to Study Oral-Drug Absorption in Man. Pharm Res 9 pp 1243-1251. 

LueBen, H.L., De Leeuw, B.J., Langemeyer, M.W., De Boer, A.G., Verhoef, J.C., and Junginger, H.E., Mucoadhesive polymers in peroral peptide drug delivery. VI. Carbomer and chitosan improve the intestinal absorption of the peptide drug buserelin in vivo, Pharm. Res., 13 1668-1672 (1996). 

Cell culture models are routinely used to assess permeability of new potential drug candidates. The simplicity and higher throughput of these models makes them a useful alternative to in vivo studies. These models are used to predict absorption in vivo, rank order compounds and examine absorption mechanism. Transcellular, paracellular, active uptake and efflux mechanisms can be studied with these models. 

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