Design of prodrugs to enhance colonic absorption by increasing lipophilicity and blocking ionization

Pharmaceuticals

Volumn 7, Issue 2, 2014, Pages 207-219

  Nofsinger, Rebecca ^a   Clas, Sophie Dorothee ^a,b   Sanchez, Rosa I ^a   Walji, Abbas ^a   Manser, Kimberly ^a   Nissley, Becky ^a   Balsells, Jaume ^a   Nair, Amrithraj ^a   Dang, Qun ^a   Bennett, David Jonathan ^a   Hafey, Michael ^a   Wang, Junying ^a   Higgins, John ^a   Templeton, Allen ^a   Coleman, Paul ^a   Grobler, Jay ^a   Smith, Ronald ^a   Wu, Yunhui ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b PharmaSolv Consulting   (United States)

Author keywords

Chemistry enabled drug delivery; Colonic absorption; Dog colonic studies; Enabling QD dosing; Enhancing lipophilicity; Prodrugs

Indexed keywords

BETA CYCLODEXTRIN SULFOBUTYL ETHER; GABAPENTIN; POLYSORBATE; PRODRUG; VERAPAMIL;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; BEAGLE; COLON ABSORPTION; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DESIGN; DRUG PENETRATION; DRUG SOLUBILITY; DRUG STABILITY; INTRACOLONIC DRUG ADMINISTRATION; IONIZATION; LIPOPHILICITY; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PLASMA CONCENTRATION-TIME CURVE; TIME TO MAXIMUM PLASMA CONCENTRATION;

EID: 84896728252     PISSN: None     EISSN: 14248247     Source Type: Journal    
DOI: 10.3390/ph7020207     Document Type: Article

References (26)

1. Dahan, A.; Khamis, M.; Agbaria, R.; Karaman, R., Targeted prodrugs in oral drug delivery: The modern molecular biopharmaceutical approach. Exp. Opin. Drug Deliv. 2012, 9, 1001-1013.
2. Huttunen, K.; Raunio, H.; Rautio, J. Prodrugs-from serendipity to rational design. Pharmacol. Rev. 2011, 63, 750-711.
3. Huttunen, K.M.; Rautio, J. Prodrugs-an efficient way to breach delivery and targeting barriers. Curr. Top. Med. Chem. 2011, 11, 2265-2287.
4. Rautio, J. Prodrugs and Targeted Delivery: Towards better ADME properties. In Methods and Principles in Medicinal Chemistry; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2011; p. 496.
5. Rautio, J.; Kumpulainen, H.; Heimbach, T.; Oliyai, R.; Oh, D.; Jaervinen, T.; Savolainen, J. Prodrugs: Design and clinical applications. Nat. Rev. Drug Discov. 2008, 7, 255-270.
6. Stella, V.J.; Borchardt, R.T.; Hageman, M.J.; Oliyai, R.; Maag, H.; Tilley, J.W. Prodrugs: Challenges and Rewards Part 1 and Part 2; Springer: New York, NY, USA, 2007; p. 726.
7. Clas, S.-D.; Sanchez, R.I.; Nofsinger, R. Chemistry-enabled drug delivery (prodrugs); recent progress and challenges. Drug Discov. Today 2014, 19, 79-87.
8. Vadlamudi, H.C.; Raju, Y.P.; Yasmenn, B.R.; Vulava, J. Anatomical biochemical and physiological consideration of the colon in design and development of novel drug delivery systems. Curr. Drug Deliv. 2012, 9, 556-565.
9. Davies, B.; Morris, T. Physiological parameters in laboratory animals and humans. Pharm. Res. 1993, 10, 1093-1095.
10. Kararli, T.T. Comparison of the gastrointestinal anatomy, physiology, and biochemistry of human and commonly used laboratory animals. Biopharm. Drug Dispos. 1995, 16, 351-380.
11. Sugano, K. Computational oral absorption simulation for low-solubility compounds. Chem. Biodivers. 2009, 6, 2014-2029.
12. Gupta, V.K.; Gnanarajan, G.; Kothiyal, P. A review article on colonic targeted drug delivery systems. Pharma Innov. 2012, 1, 14-24.
13. Patel, G.N.; Patel, G.C.; Patel, R.B.; Patel, S.S.; Patel, J.K.; Bharadia, P.D.; Madhabhai, M. Oral colon-specific drug delivery: An overview. Drug Deliv. Technol. 2006, 6, 62-71.
14. Sareen, R.; Jain, N.; Dhar, K.L. An insight to colon targeted drug delivery systems. Drug Deliv. Lett. 2013, 3, 127-135.
15. Moss, D.M.; Siccardi, M.; Murphy, M.; Piperakis, M.M.; Khoo, S.H.; Back, D.J.; Owen, A. Divalent metals and pH alter raltegravir disposition in vitro. Antimicrob. Agents Chemother. 2012, 56, 3020-3026.
16. Laine, K.; Huttunen, K. Enzyme-Activated Prodrug Strategies for Site-Selective Drug Delivery. In Methods and Principles in Medicinal Chemistry: Prodrugs and Targeted Delivery; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2011; Volume 47, pp. 231-252.
17. Moridani, M.Y. Reducing Presystemic Drug Metabolism. In Methods and Principles in Medicinal Chemistry: Prodrugs and Targeted Delivery; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2011; Volume 47, pp. 207-230.
18. Malik, K.; Goswami, L.; Kothiyal, P.; Maukhopadhyay, S. A review on colon targeting drug delivery systems: Novel approaches, anatomy and evaluation. Pharma Innov. 2012, 1, 1-12.
19. Cundy, K.C.; Sastry, S.; Luo, W.; Zou, J.; Moors, T.L.; Canafax, D.M. Clinical pharmacokinetics of xp13512, a novel transported prodrug of gabapentin. J. Clin. Pharmacol. 2008, 48, 1378-1388.
20. Nofsinger, R.; Borchardt, R.T. Factors that restrict the cell permeation of cyclic prodrugs of an opioid peptide, part 4: Characterization of the biopharmaceutical and physicochemical properties of two new cyclic prodrugs design to be stable to oxidative metabolism by cytochrome p-450 enzyme in the intestinal mucosa. J. Pharm. Sci. 2012, 101, 3500-3510.
21. Palm, K.; Luthman, K.; Ros, J.; Grasjo, J.; Artursson, P. Effect of molecular charge on intestinal epithelial drug transport: pH-dependent transport of cationic drugs. J. Pharmacol. Exp. Ther. 1999, 291, 435-443.
22. Masayuki, A.; Atsushi, F.; Tohru, M.; Keni, Y.; Toshio, S.; Hiroyasu, O. Evaluation of sustained-release granules of chlorphenesin carbamate in dogs and humans. Int. J. Pharm. 1993, 100, 133-142.
23. Sinko, P.J.; Sutyak, J.P.; Leesman, G.D.; Hu, P.; Makhey, V.D.; Yu, H.; Smith, C.L. Oral absorption of anti-aids nucleoside analogues: 3. Regional absorption and in vivo permeability of 2′,3′-dideoxyinosine in an intestinal-vascular access port (ivap) dog model. Biopharm. Drug Dispos. 1997, 18, 197-710.
24. Sutton, S.C.; Evans, L.A.; Fortner, J.H.; McCarthy, J.M.; Sweeney, K. Dog colonoscopy model for predicting human colon absorption. Pharm. Res. 2006, 23, 1554-1563.
25. Vertzoni, M.; Diakidou, A.; Chatzilia, M.; Soederlind, E.; Abrahamsson, B.; Dressman, J.B.; Reppas, C. Biorelevant media to simulate fluids in the ascending colon of humans and their usefulness in predicting intracolonic drug solubility. Pharm. Res. 2010, 27, 2187-2196.
26. He, H.; Lyons, K.; Shen, X.; Yao, Z.; Bleasby, K.; Chan, G.; Hafey, M.; Li, X.; Xu, S.; Salituro, G.; et al. Utility of unbound plasma drug levels and p-glycoprotein transport data in prediction of central nervous system exposure. Xenobiotica 2009, 39, 687-693.