Research of oral prodrugs:opportunities and challenges

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CAO Feng()
PING Qi-neng()
CHEN Jun()
Journal Title:
Volume 43, Issue 04, 2008
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  • [1]Gomez-Orellana I.Strategies to improve oral drug bioavailability[J].Expert Opin Drug Deliv,2005,2:419 -433.
  • [2]Fahr A,Liu X.Drug delivery strategies for poorly watersoluble drugs[J].Expert Opin Drug Deliv,2007,4:403-416.
  • [3]Ettmayer P,Amidon GL,Clement B,et al.Lessoms learned from marketed and investigational prodrugs[J].J Med Chem,2004,47:2393 -2404.
  • [4]Beaumont K,Webster R,Gardner I,et al.Design of ester prodrugs to enhance oral absorption of poorly permeable compounds:challenges to the discovery scientist[J].Curr Drug Metab,2003,4:461-485.
  • [5]Djaldetti R,Inzelberg R,Giladi N,et al.Oral solution of levodopa ethylester for treatment of response fluctuations in patients with advanced Parkinson' s disease[J].Mov Disord,2002,17:297-302.
  • [6]Brouwers J,Tack J,Augustijns P.In vitro behavior of a phosphate ester prodrug of amprenavir in human intestinal fluids and in the Caco-2 system:illustration of intraluminal supersaturation[J].Int J Pharm,2007,336:302-309.
  • [7]Cho H,Chung Y.Water soluble cyclosporine monomethoxy poly (ethyleneglycol) conjugates as potential prodrugs[J].Arch Pharm Res,2004,27:662-669.
  • [8]Stella V J,Nti-Addae KW.Prodrug strategies to overcome poor water solubility[J].Adv Drug Deliv Rev,2007,59:677-694.
  • [9]Abrams WB,Davies RO,Gomez HJ.Clinical pharmacology of enalapril[J].J Hypertens Suppl,1984,2:S31-36.
  • [10]Williams PE,Brown AN,Rajaguru S,et al.The pharmacokinetics and bioavailability of cilazapril in normal man[J].Br J Clin Pharmacol,1989,27(Suppl.2):181S-188S.
  • [11]Nakamura M,Kawakita Y,Yasuhara A,et al.In vitro and in vivo evaluation of the metabolism and bioavailability of ester prodrugs of mgs0039 (3-(3,4-dichlorobenzyloxy)-2-amino-6-fluorobicyclo[3.1.0] hexane-2,6-dicarboxylic acid),a potent metabotropic glutamate receptor antagonist[J].Drug Metab Dispos,2006,34:369-374.
  • [12]Borchardt RT.Optimizing oral absorption of peptides using prodrug strategies[J].J Control Release,1999,62:231-238.
  • [13]Pauletti GM,Gangwar S,Siahaan TJ.Improvement of oral peptide bioavailability:peptidomimetics and prodrug strategies[J].Adv Drug Deliv Rev,1997,27:235 -256.
  • [14]Cao F,Guo JX,Ping QN,et al.Ester prodrug of scuteUar in:synthesis,physicochemical property and degradation[J].Acta Pharm Sin (药学学报),2006,41:595 -602.
  • [15]Tunek A,Levin E,Svensson LA.Hydrolysis of 3H bambuterol,a carbamate prodrug of terbutaline,in blood from humans and laboratory animals in vitro[J].Biochem Pharmacol,1988,37:3867-3876.
  • [16]Bodor N,Buchwald P.Recent advances in the brain targeting of neuropharmaceuticals by chemical delivery systems[J].Adv Drug Deliv Rev,1999,36:229-254.
  • [17]Ettmayer P,Amidon GL,Clement B,et al.Lessons learned from marketed and investigational prodrngs[J].J Med Chem,2004,47:2393-2404.
  • [18]Lambert DM.Rationale and applications of lipids as prodrug carriers[J].Eur J Pharm Sci,2000,11 (Suppl 2):S15 -27.
  • [19]Van den Mooter G.Colon drug delivery[J].Expert Opin Drug Deliv,2006,3:111-125.
  • [20]Hwang JJ,Marshall JL.Capecitabine:fulfilling the promise of oral chemotherapy[J].Expert Opin Pharmacother,2002,3:733-743.
  • [21]Han HK,Amidon GL.Targeted prodrug design to optimize drug delivery[J].AAPS Pharm Sci,2000,2:E6.
  • [22]Giles F,Estey E,O'Brien S.Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia[J].Cancer,2003,98:2095-2104.
  • [23]Ware JA.Membrane transporters in drug discovery and development:a new mechanistic ADME era[J].Mol Pharm,2006,3:1 -2.
  • [24]Dietrich CG,Geier A,Oude Elferink RP.ABC of oral bioavailability:transporters as gatekeepers in the gut[J].Gut,2003,52:1788-1795.
  • [25]Anand BS,Dey S,Mitra AK.Current prodrug strategies via membrane transporters/receptors[J].Expert Opin Biol Ther,2002,2:607-620.
  • [26]Steffansen B,Nielsen CU,Brodin B,et al.Intestinal solute carriers:an overview of trends and strategies for improving oral drug absorption[J].Eur J Pharm Sci,2004,21:3-16.
  • [27]Jain R,Duvvnri S,Kansara V,et al.Intestinal absorption of novel-dipeptide prodrugs of saquinavir in rats[J].Int J Pharm,2007,336:233 -240.
  • [28]Rubio-Aliaga I,Daniel H.Mammalian peptide transporters as targets for drug delivery[J].Trends Pharmacol Sci,2002,23:434-440.
  • [29]Ganapathy ME,Brandsch M,Prasad PD,et al.Differential recognition of beta-lactam antibiotics by intestinal and renal peptide transporters,PEPT 1 and PEPT 2[J].J Biol Chem,1995,270:25672-25677.
  • [30]Terada T,Sawada K,Irie M,et al.Structural requirements for determining the substrate affinity of peptide transporters PEPTI and PEPT2[J].Pflugers Arch,2000,440:679-684.
  • [31]Beauchamp LM,Drr GF,de Miranda P,et al.Amino acid ester prodrugs of acyclovir[J].Antiviral Chem Chemother,1992,3:157-164.
  • [32]Han H,de Vrueh RL,Rhie JK,et al.5'-Amino acid esters of antiviral nucleosides,acyclovir,and AZT are absorbed by the intestinal PEPT1 peptide transporter.[J].Pharm Res,1998,15:1154-1159.
  • [33]Sawada K,Terada T,Saito H,et al.Recognition of Lamino acid ester compounds by rat peptide transporters PEPT1 and PEPT2[J].J Pharmacol Exp Ther,1999,291:705-709.
  • [34]Englund G,Rorsman F,Ronnblom A,et al.Regional levels of drug transporters along the human intestinal tract:co-expression of ABC and SLC transporters and comparison with Caco-2 cells[J].Eur J Pharm Sci,2006,29:269-277.
  • [35]Jain R,Duvvuri S,Kansara V,et al.Intestinal absorption of novel-dipeptide prodrugs of saquinavir in rats[J].Int J Pharm,2007,336:233 -240.
  • [36]Testa B.Prodrug research:futile or fertile?[J].Biochem Pharmacol,2004,68:2097-2106.
  • [37]Van Gelder J,Shafiee M,De Clercq E,et al.Speciesdependent and site-specific intestinal metabolism of ester prodrugs[J].Int J Pharm,2000,205:93-100.
  • [38]Yoshigae Y,Imai T,Aso T,et al.Species differences in the disposition of propranolol prodrugs derived from hydrolase activity in intestinal mucosa[J].Life Sci,1998,62:1231-1241.
  • [39]Minagawa T,Kohno Y,Suwa T,et al.Species differences in hydrolysis of isocarbacyelin methyl ester (TEI-9090) by blood esterases[J].Biochem Pharmacol,1995,49:1361-1365.
  • [40]Liederer BM,Borchardt RT.Stability of oxymethylmodified coumarinic acid cyclic prodrugs of diastereomeric opioid peptides in biological media from various animal species including human[J].J Pharm Sci,2005,94:2198-2206.
  • [41]Katoh M,Suzuyama N,Takeuchi T,et al.Kinetic analyses for species differences in P-glycopruteinmediated drug transport[J].J Pharm Sci,2006,95:2673-2683.
  • [42]Suzuyama N,Katoh M,Takeuchi T,et al.Species differences of inhibitory effects on P-glycoproteinmediated drug transport[J].J Pharm Sci,2007,96:1609-1618.
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