Absorption prediction

Norinder, U Haeberlein, M. Calculated molecular properties and multivariate statistical analysis in absorption prediction. 

The intrinsic membrane permeabilities in Table 7.15 span about eight orders of magnitude, whereas the effective (measured in the in vitro assay) permeabilities are confined to a much narrower range, limited by the UWL. Since the in vivo UWL in the gut is estimated to be about 50 pm [541], it is more appropriate to use Pm than Pe values in oral absorption prediction strategies. 

Kramer, S. D., Absorption prediction from physicochemical parameters, Pharm. Sci. Tech. Today 2, 373-380 (1999). 

Dressman, J. B. Lennemas, H. (eds.), Oral Drug Absorption—Prediction and Assessment, Marcel Dekker, New York, 2000. 

Oral Drug Absorption Prediction and Assessment, edited by Jennifer B. Dressman and Hans Lennernas... 

Calculated Molecular Properties and Multivariate Statistical Analysis in Absorption Prediction... 

Rifaximin appears to be an ideal agent for the treatment of infectious watery diarrhea. It has shown excellent efficacy in numerous clinical trials of bacterial diarrhea. Its excellent side effect profile and lack of systemic absorption predict that it should be useful in treating hosts for whom the currently favored fluoroquinolones are contraindicated. Uses limited to enteric indications and its inherently low propensity to induce sustainable resistance among Gram-negative flora favor the sustained usefulness of rifaximin in the treatment of enteric syndromes. 

Dressman JB. Dissolution testing of immediate-release products and its application to forecasting in vivo performance. In Dressman JB, Lennemas H, eds. Oral Drug Absorption Prediction and Assessment. New York Marcel Dekker, 2000 155-181. 

Lennernas H (2000) Animal Perfusion Studies. In JB Dressman, H Lennernas (Eds.), Oral Drug Absorption Prediction and Assessment. New York, NY, Dekker, Inc. pp 73-98. 

Lead optimization of new chemical entities (NCEs) based on pharmacokinetic behavior plays a major role in modern drug discovery. Despite advancement of drug delivery methods, the oral route remains the most frequent route of administration for approved new drugs. Therefore, during lead optimization it is essential to identify NCEs with sufficient oral absorption predicted using a variety of in vitro and in vivo assays. It is well recognized that in order for a NCE to achieve reasonable oral absorption, it will need to have adequate aqueous solubility, as well as intestinal permeability [1], Recent advancements in chemistry, such as parallel and combinatorial synthesis, have resulted in a multifold increase in the number of compounds that are available for evaluation in new drug discovery. Furthermore, a variety of improved structural chemistry... 

Hendriksen BA, Sanchez Felix MV, Bolger MB (2003) The composite solubility versus pH profile and its role in intestinal absorption prediction. AAPS PharmSci. 5 35 19. 

Van de Waterbeemd H, In Oral Drug Absorption. Prediction and Assessment, Dekker, New York, Eds. Dressman J, Lennernas, H, pp. 31-49. 

In a recent review of pharmacokinetics in drug discovery, Ruiz-Garcia et al. [81] compiled an exhaustive list of software resources for absorption prediction. The main topic in the described databases is transporters, in particular the ATP-binding cassette, of which the efflux transporter P-gp and the peptide transporter PEPTl are well known examples. These examples show that science is moving away from the simplistic passive transport view of permeability and towards an all-inclusive, mechanism-understanding model of absorption, which takes account of all the interactions between the agents involved in the specific permeation process. 

---