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1,161 results on '"Amidon, Gordon L."'

118. Membrane topology of the human dipeptide transporter hPEPT1, determined by epitope insertions

Author

Covitz, Kuang-Ming Y., Amidon, Gordon L., and Sadee, Wolfgang.

Subjects
Absorption -- Research, Antigenic determinants -- Observations, Biochemistry -- Research, Biological sciences, Chemistry
Abstract

Intestinal transporters are important in nutrient uptake and in mediating drug absorption. The human intestinal transporter hPEPT1 is a mediator in the absorption of dipeptides and tripeptides. The presence of 12 putative TMDs is suggested by the hydropathy plot of hPEPT1, although the hydropathy profile does not establish the amount and location of TMDs with certainty. The topology of hPEPT1 has been tested through insertion of epitope tags into intra or extracellular loops, to determine accessibilty tl anti-epitope antibodies.

Published
1998

131. Design of compounds that increase the absorption of polar molecules

Author

Bowe, Caryn Lang, Mokhtarzadeh, Leila, Venkatesan, Pushpa, Babu, Suresh, Axelrod, Helena R., Sofia, Michael J., Kakarla, Ramesh, Chan, Tin Yau, Kim, Jae Seung, Lee, Hye J., Amidon, Gordon L., Choe, Sally Y., Walker, Suzanne, and Kahne, Daniel

Subjects
Absorption -- Research, Bile acid metabolism -- Research, Science and technology
Abstract

Hydrophilic drugs are often poorly absorbed when administered orally. There has been considerable interest in the possibility of using absorption enhancers to promote absorption of polar molecules across membrane surfaces. The bile acids are one of the most widely investigated classes of absorption enhancers, but there is disagreement about what features of bile acid enhancers are responsible for their efficacy. We have designed a class of glycosylated bile acid derivatives to evaluate how increasing the hydrophilicity of the steroid nucleus affects the ability to transport polar molecules across membranes. Some of the glycosylated molecules are significantly more effective than taurocholate in promoting the intestinal absorption of a range of drugs, showing that hydrophobicity is not a critical parameter in transport efficacy, as previously suggested. Furthermore, the most effective glycosylated compound is also far less damaging to membranes than the best bile acid absorption promoters, presumably because it is more hydrophilic. The results reported here show that it is possible to decouple absorption-promoting activity from membrane damage, a finding that should spark interest in the design of new compounds to facilitate the delivery of polar drugs.

Published
1997

132. Ultrathin, Large-Area Membrane Diffusion Cell for pH-Dependent Simultaneous Dissolution and Absorption Studies

Author

Sinko, Patrick D., Harris, Sarah, Salehi, Niloufar, Meyer, Pamela J., Amidon, Gordon L., Amidon, Gregory E., Sinko, Patrick D., Harris, Sarah, Salehi, Niloufar, Meyer, Pamela J., Amidon, Gordon L., and Amidon, Gregory E.

Abstract

Preclinical evaluation of modern oral dosage forms requires more advanced in vitro devices as the trend of selecting low solubility, high permeability compounds for commercial development continues. Current dissolution methodologies may not always be suitable for such compounds due to excessive fluid volume, high fluid shear rates, heterogeneity of shear rates, suboptimal fluid flow, and, ultimately, the lack of absorption ability (Gray et al. The Science of USP 1 and 2 Dissolution: Present Challenges and Future Relevance; Pharmaceutical Research, 2009; Vol. 26; pp 1289-1302). Herein, a new dissolution apparatus is introduced in combination with an ultrathin, semipermeable polymer membrane that mimics human passive absorption for lipophilic compounds. The ultrathin large-area polydimethylsiloxane (PDMS) membrane (UTLAM) absorption system is designed to mimic the dissolution and passive transcellular diffusion process representing the oral absorption pathway. A simple spin-casting method was developed to fabricate the ultrathin highly uniform membranes. To minimize membrane resistance to diffusion and maximize transport across the polymer membrane, 10-40 mu m PDMS membranes were successfully prepared. A new diffusion cell was designed and tested to support the UTLAM and incorporates a hydrofoil impeller for more desirable hydrodynamics and mixing, using ibuprofen as a model weak acidic drug. UTLAM permeability was sufficiently high that the aqueous boundary layer contributed to the overall permeability of the system. This diffusion cell system demonstrated that, when the aqueous diffusion layer contributes to the overall resistance to transport, the pH at which absorption is 50% of maximum (pH(50)(%)) shifts from the pK(a) to higher values, demonstrating why weak acid drugs can exhibit high absorption at pH's significantly greater than their pK(a). High rates of transport across the UTLAM are possible for drugs with high partition coefficients (i.e., BCS II compounds

Published
2020
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