Transport of levovirin prodrugs in the human intestinal Caco-2 cell line

Journal of Pharmaceutical Sciences

Volumn 95, Issue 6, 2006, Pages 1318-1325

  Li, Fujun ^a   Hong, Lei ^a   Mau, Cheng I ^a   Chan, Rebecca ^a   Hendricks, Than ^a   Dvorak, Chuck ^a   Yee, Calvin ^a   Harris, Jason ^a   Alfredson, Tom ^a  

^a ROCHE BIOSCIENCE   (United States)

Author keywords

Caco 2 cells; Hepatitis C; Levovirin; Peptide transporters; Permeability; Prodrugs; Transport

Indexed keywords

AMINO ACID DERIVATIVE; CEFALEXIN; ENALAPRIL; GLYCOSARCOSINE; LEVOVIRIN; LEVOVIRIN 2',3' BIS VALINE; LEVOVIRIN 5' ALANINE; LEVOVIRIN 5' ISOLEUCINE; LEVOVIRIN 5' LEUCINE; LEVOVIRIN 5' PHENYLALANINE; LEVOVIRIN 5' PROLYLVALINE; LEVOVIRIN 5' SARCOSINE; LEVOVIRIN 5' VALINE; LEVOVIRIN 5' VALYLPROLINE; PEPTIDE TRANSPORTER 1; PRODRUG; R 1518; RIBAVIRIN; UNCLASSIFIED DRUG; VALGANCICLOVIR;

ACTIVE TRANSPORT; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CELL STRAIN CACO 2; COMPETITIVE INHIBITION; CONTROLLED STUDY; DRUG COMPETITION; DRUG EFFECT; DRUG PENETRATION; DRUG SCREENING; DRUG STABILITY; DRUG STRUCTURE; DRUG TRANSPORT; HUMAN; HUMAN CELL; HUMAN EXPERIMENT; NONHUMAN; PH; RAT;

EID: 33745017670     PISSN: 00223549     EISSN: 15206017     Source Type: Journal    
DOI: 10.1002/jps.20434     Document Type: Article

References (26)

1. Keating GM, Curran MP. 2003. Peginterferon-alpha-2a (40 kD) plus ribavirin: A review of its use in the management of chronic hepatitis C. Drugs 63:701-730.
2. Tam RC, Ramasamy K, Bard J, Pai B, Lim C, Averett DR. 2000. The ribavirin analogue ICN 17261 demonstrates reduced toxicity and antiviral effects with retention of both immunomodulatory activity and reduction of hepatitis-induced serum alanine aminotransferase levels. Antimicrob Agents Chemother 44:1276-1283.
3. Lin CC, Luu T, Lourenco D, Yeh LT, Lau JYN. 2003. Absorption, pharmacokinetics and excretion of levovirin in rats, dogs and cynomolgus monkeys. J Antimicrob Chemother 51:93-99.
4. Huang Y, Ostrowitzki S, Hill G, Navarro M, Berger N, Kopeck P, Mau CI, Alfredson T, Lal R. 2005. Single- and multiple-pharmacokinetics of levovirin valinate hydrochloride (R1518) in healthy volunteers. J Clin Pharmacol 45:578-588.
5. +-nucleoside purine (N1) transporter. Pharm Res 15:950-952.
6. +-independent transport systems in T84 and Caco-2 cells. Biochim Biophys Acta 1419:15-22.
7. Charman WN, Porter CJH. 1996. Lipophilic prodrugs designed for intestinal lymphatic transport. Adv Drug Deliv Rev 19:149-169.
8. Fleisher D, Bong R, Stewart BH. 1996. Improved oral drug delivery: Solubility limitations overcome by the use of prodrugs. Adv Drug Deliv Rev 19:115-130.
9. Ettmayer P, Amidon GL, Clement B, Testa B. 2004. Lessons learned from marketed and investigational prodrugs. J Med Chem 47:1-12.
10. Balimane PV, Tamai I, Guo A, Nakanishi T, Kitada H, Leibach FH, Tsuji A, Sinko PJ. 1998. Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir. Biochem Biophys Res Commun 250:246-251.
11. Sawada K, Terada T, Saito H, Hashimoto Y, Inui KI. 1999. Recognition of L-amino acid ester compounds by rat peptide transporters PEPT1 and PEPT2. J Pharmacol Exp Ther 291:705-709.
12. Rubio-Aliaga I, Daniel H. 2002. Mammalian peptide transporters as targets for drug delivery. Trends Pharmacol Sci 23:434-440.
13. Ganapathy ME, Huang W, Wang H, Ganapathy V, Leibach FH. 1998. Valacyclovir: A substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Biochem Biophys Res Commun 246:470-475.
14. Sinko PJ, Balimane PV. 1998. Carrier-mediated intestinal absorption of valacyclovir, the L-valyl ester prodrug of acyclovir. 1. Interactions with peptides, organic anions and organic cations in rats. Biopharm Drug Dispos 19:209-217.
15. de Vrueh RL, Smith PL, Lee CP. 1998. Transport of L-valine-acyclovir via the oligopeptide transporter in the human intestinal cell line, caco-2. J Pharmacol Exp Ther 286:1166-1170.
16. Sugawara M, Huang W, Fei YJ, Leibach FH, Ganapathy V, Ganapathy ME. 2000. Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2. J Pharm Sci 89:781-789.
17. Brown F, Banken L, Saywell K, Arum I. 1999. Pharmacokinetics of valganciclovir and ganciclovir following multiple oral dosages of valganciclovir in HIV- and CMV-seropositive volunteers. Clin Pharmacokinet 37:167-176.
18. Han H, de Vrueh RL, Rhie JK, Covitz KM, Smith PL, Lee CP, Oh DM, Sadee W, Amidon GL. 1998. 5′-amino acid esters of antiviral nucleosides, acyclovir, and AZT are absorbed by the intestinal PEPT1 peptide transporter. Pharmaceutical Res 15:1154-1159.
19. Han HK, Oh DM, Amidon GL. 1998. Cellular uptake mechanism of amino acid ester prodrugs in Caco-2/hPEPT1 cells overexpressing a human peptide transporter. Pharm Res 15:1382-1386.
20. Boll M, Herget M, Wagener M, Weber WM, Markovich D, Biber J, Clauss W, Murer H, Daniel H. 1996. Expression cloning and functional characterization of the kidney cortex high-affinity proton-coupled peptide transporter. Proc Natl Acad Sci USA 93:284-289.
21. Saito H, Inui K. 1993. Dipeptide transporters in apical and basolateral membranes of the human intestinal cell line Caco-2. Ameri Physio Society 265:G289-G294.
22. Walker D, Thwaites DT, Simmons NL, Gilbert HJ, Hirst BH. 1998. Substrate upregulation of the human small intestinal peptide transporter, hPepT1. J Physiol 507:697-706.
23. Abe H, Satoh M, Miyauchi S, Shuto S, Matsuda A, Kamo N. 1999. Conjugation of dipeptide to fluorescent dyes enhances its affinity for a dipeptide transporter (PEPT1) in human intestinal Caco-2 cells. Bioconjugate Chem 10:24-31.
24. Temple CS, Boyd CA. 1998. Proton-coupled oligopeptide transport by rat renal cortical brush border membrane vesicles: A functional analysis using ACE inhibitors to determine the isoform of the transporter. Biochim Biophys Acta 1373:277-281.
25. Chu XY, Sanchez-Castano GP, Higaki K, Oh DM, Hsu CP, Amidon GL. 2001. Correlation between epithelial cell permeability of cephalexin and expression of intestinal oligopeptide transporter. J Pharmacol ExpTher 299:575-582.
26. Mau C, Liu H, Tran T, Young M, Ahene A, Tarnowski T, Alfredson T, Huang Y, Lal R. 2004. Pharmacokinetic studies of levovirin valinate hydrochloride (R1518) in mice, rats, monkeys, and humans. 7th International ISSX Meeting. August.