Regional Intestinal Drug Permeability and Effects of Permeation Enhancers in Rat
Abstract
1. Introduction
2. Materials and Methods
2.1. Active Pharmaceutical Ingredients, Pharmaceutical Excipients and Other Chemicals
2.2. Study Formulations
2.3. Animals and Study Design
2.4. Determination of Blood-to-Lumen Jejunal 51Cr-EDTA Clearance (CLCr-EDTA)
2.5. Bioanalysis
2.6. Intestinal Effective Permeability (Peff) Calculation
2.7. Statistical Analysis
3. Results
3.1. Plasma Profiles
3.2. Lumen-to-Blood Effective Permeability (Peff) of Model Drugs
3.3. Blood-to-Lumen CLCr-EDTA Ratio
4. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Compounds (BCS Class) | MM (g/mol) | pKa | PSA | HBA/HBD | Log P | Log D7.4 | Log D6.5 |
---|---|---|---|---|---|---|---|
Atenolol (III) | 266 | 9.6 b | 88.1 | 4/4 | 0.18 | −2.0 | <−2.0 |
Enalaprilat (III) | 348 | 3.17 b/7.84 a | 102.1 | 6/3 | −0.13 | −1.0 | −1.0 |
Metoprolol (I) | 267 | 9.6 b | 57.8 | 4/2 | 2.07 | 0.0 | −0.5 |
Ketoprofen (II) | 254 | 3.89 a | 54.2 | 3/1 | 3.37 | 0.1 | 0.8 |
Conditions | Plasma Appearance Peff (×10–4 cm/s) | |||
---|---|---|---|---|
Atenolol | Enalaprilat | Ketoprofen | Metoprolol | |
Jejunum pH 6.5 | 0.022 ± 0.01 | 0.005 ± 0.004 | 1.5 ± 1.1 | 0.28 ± 0.24 |
Jejunum pH 7.4 | 0.016 ± 0.005 | 0.004 ± 0.001 | 0.64 ± 0.15 | 0.17 ± 0.095 |
Colon pH 6.5 | 0.015 ± 0.007 | 0.009 ± 0.007 | 1.1 ± 0.3 | 0.41 ± 0.19 |
Colon pH 7.4 | 0.011 ± 0.005 | 0.006 ± 0.004 | 0.73 ± 0.14 | 0.38 ± 0.15 |
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Dahlgren, D.; Cano-Cebrián, M.-J.; Olander, T.; Hedeland, M.; Sjöblom, M.; Lennernäs, H. Regional Intestinal Drug Permeability and Effects of Permeation Enhancers in Rat. Pharmaceutics 2020, 12, 242. https://doi.org/10.3390/pharmaceutics12030242
Dahlgren D, Cano-Cebrián M-J, Olander T, Hedeland M, Sjöblom M, Lennernäs H. Regional Intestinal Drug Permeability and Effects of Permeation Enhancers in Rat. Pharmaceutics. 2020; 12(3):242. https://doi.org/10.3390/pharmaceutics12030242
Chicago/Turabian StyleDahlgren, David, Maria-Jose Cano-Cebrián, Tobias Olander, Mikael Hedeland, Markus Sjöblom, and Hans Lennernäs. 2020. "Regional Intestinal Drug Permeability and Effects of Permeation Enhancers in Rat" Pharmaceutics 12, no. 3: 242. https://doi.org/10.3390/pharmaceutics12030242
APA StyleDahlgren, D., Cano-Cebrián, M.-J., Olander, T., Hedeland, M., Sjöblom, M., & Lennernäs, H. (2020). Regional Intestinal Drug Permeability and Effects of Permeation Enhancers in Rat. Pharmaceutics, 12(3), 242. https://doi.org/10.3390/pharmaceutics12030242