The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
High-Throughput Permeability pH Profile and High-Throughput Alkane/Water log P with Artificial Membranes
Abstract
This study reports on a novel, high-throughput assay, designed to predict passive, transcellular permeability in early drug discovery. The assay is carried out in 96-well microtiterplates and measures the ability of compounds to diffuse from a donor to an acceptor compartment which are separated by a 9-10 microm hexadecane liquid layer. A set of 32 well-characterized, chemically diverse drugs was used to validate the method. The permeability values derived from the flux factors between donor and acceptor compartments show a good correlation with gastrointestinal absorption in humans. For comparison, correlations based on experimental or calculated octanol/water distribution coefficients (log D(o/w,6.8)) were significantly lower. In addition, this simple and robust assay allows determination of pH permeability profiles, critical information to predict gastrointestinal absorption of ionizable drugs and difficult to obtain from cell culture experiments. Correction for the unstirred water layer effect allows to differentiate between effective and intrinsic membrane permeability and opens up the dynamic range of the method. In addition, alkane/water partition coefficients can be derived from intrinsic membrane permeabilities, making this assay the first high-throughput method able to measure alkane/water log P in the microtiterplate format.
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Citations
Cites
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Permeability of small nonelectrolytes through lipid bilayer membranes
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Cited by
Molecular properties that influence the oral bioavailability of drug candidates
Veber, D. F., Johnson, S. R., Cheng, H.-Y., Smith, B. R., Ward, K. W., & Kopple, K. D. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm020017n · Cited by 8,420
High throughput artificial membrane permeability assay for blood–brain barrier
Di, L., Kerns, E. H., Fan, K., McConnell, O. J., & Carter, G. T. (2003) · European Journal of Medicinal Chemistry · doi:10.1016/s0223-5234(03)00012-6 · Cited by 1,195
Physicochemical Profiling (Solubility, Permeability and Charge State)
Avdeef, A. (2001) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026013395100 · Cited by 587
Zhu, C., Jiang, L., Chen, T.-M., & Hwang, K.-K. (2002) · European Journal of Medicinal Chemistry · doi:10.1016/s0223-5234(02)01360-0 · Cited by 351
PAMPA—critical factors for better predictions of absorption
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Self-citationDahan, A., Miller, J. M., Hoffman, A., Amidon, G. E., & Amidon, G. L. (2010) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22033 · Cited by 224
Drug permeability profiling using cell-free permeation tools: overview and applications
Berben, P., Bauer-Brandl, A., Brandl, M., Faller, B., Flaten, G. E., Jacobsen, A.-C., Brouwers, J., & Augustijns, P. (2018) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2018.04.016 · Cited by 199
Self-citationNeumann, U., Rueeger, H., Machauer, R., Veenstra, S. J., Lueoend, R. M., Tintelnot-Blomley, M., Laue, G., Beltz, K., Vogg, B., Schmid, P., et al. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0033-8 · Cited by 113
Lübtow, M. M., Haider, M. S., Kirsch, M., Klisch, S., & Luxenhofer, R. (2019) · Biomacromolecules · doi:10.1021/acs.biomac.9b00618 · Cited by 111
Chalupova, K., Korabecny, J., Bartolini, M., Monti, B., Lamba, D., Caliandro, R., Pesaresi, A., Brazzolotto, X., Gastellier, A.-J., Nachon, F., et al. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.02.021 · Cited by 118
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Wang, Z., Hu, J., Yang, X., Feng, X., Li, X., Huang, L., & Chan, A. S. C. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01417 · Cited by 91
Evaluation of the GastroPlus™ Advanced Compartmental and Transit (ACAT) Model in Early Discovery
Gobeau, N., Stringer, R., De Buck, S., Tuntland, T., & Faller, B. (2016) · Pharmaceutical Research · doi:10.1007/s11095-016-1951-z · Cited by 67
Self-citationTuning the predictive capacity of the PAMPA-BBB model
Müller, J., Esső, K., Dargó, G., Könczöl, Á., & Balogh, G. T. (2015) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2015.08.019 · Cited by 46
Machauer, R., Lueoend, R., Hurth, K., Veenstra, S. J., Rueeger, H., Voegtle, M., Tintelnot-Blomley, M., Rondeau, J.-M., Jacobson, L. H., Laue, G., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01300 · Cited by 40
Pharmacokinetics and metabolism of SRX246: a potent and selective vasopressin 1a antagonist
Fabio, K. M., Guillon, C. D., Lu, S.-F., Heindel, N. D., Brownstein, M. J., Lacey, C. J., Garippa, C., & Simon, N. G. (2013) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.23495 · Cited by 34
Turgutalp, B., Bhattarai, P., Ercetin, T., Luise, C., Reis, R., Gurdal, E. E., Isaak, A., Biriken, D., Dinter, E., Sipahi, H., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01003 · Cited by 27
Metadata
- Authors
- Wohnsland, F., & Faller, B.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2001-02-03
- Volume
- 44
- Issue
- 6
- Pages
- 923-930
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2073101936
- Cited by
- 492
- References
- 3
- FWCI
- 13.72
- Type
- journal article
- Language
- en
- Open access
- closed
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