OCULAR DISPOSITION OF ACYCLOGUANOSINE ANALOGUES

Summary

Principal Investigator: Ashim Mitra
Affiliation: University of Missouri-Kansas City
Country: USA
Abstract: The broad overall objective of this research is to enhance drug delivery to the anterior segment of the eye. More specifically the goal of this research is to develop acycloguanosine analogues of greater efficacy and reduced toxicities in the treatment of necrotising herpes simplex and cytomegalovirus macular and peripheral iritis, uveitis and retinitis in AIDS patients. Acycloguanosine analogues have low thermodynamic activity or escaping tendency from the aqueous phase into the lipid biophase. The specific aim will be achieved via the synthesis of a series of lipophilic bioreversible analogues. A series of 3', 5'-diesters of ganciclovir and 3'- monoesters of acyclovirwill be synthesized comprising of 1) a homologous series of aliphatic esters: propionate, butyrate and valerate, 2) branched chain aliphatic esters: pivaloate, isobutyrate, 3) aromatic esters: benzoate, p methoxy, p-nitro benzoates and 4) alicyclic ester: 1-adamantoate. The compounds are purified by recrystallization from methanol-chloroform mixture and purity is checked by HPLC. TLC and by melting point on two successive crystallizations. Characterization of these compounds will be made with respect to their l.R., N.M.R., mass spec. melting points, aqueous solubilities and octanoliwater partition coefficients. The in-vitro kinetics of chemical and enzymatic regeneration of the parent drugs will be studied using appropriate media and tissue homogenates. Evaluation of the rates of permeation across the rabbit corena will be made. The transfer, disposition and bioconversion of these compounds from both topical and intravitreal delivery will also be defined. These novel prodrugs are expected to permeate more rapidly and to a greater extent into the ocular tissues and nerve cells than parent acyclovir or ganciclovir. The pharmacokinetic and disposition characteristic studies of the analogues will result in the identification of a compound with optimal therapeutic potential. the distribution of the esters, regenerated parent drug and any phosphate metabolite in the plasma, aqueous humor, cornea, lens, iris ciliary body, vitreous and retinal tissues will be measured at (1) at different time points following topical administration of 50 microL volume of the same molar concentration of each compound (2) at different time points following intravitreal injection of the same molar equivalent doses of all compounds. Preliminary experiments just performed in our laboratory revealed that 50 microL of a 1 mM topical dosing of acyclovir-3'-valerate produced an aqueous humor acyclovir level of 25.99 microM at 30 mins post instillation compared to 6.25 microM concentration from a molar equivalent dose of the parent drug acyclovir. The parent drug is the only chemical species observed in the ocular fluids at 30 mins following topical dosing of the 3'- valerate analogue. The antiviral efficacies of three pharmacokinetically optimized analogues in each series (acyclovir and ganciclovir) will be evaluated in virus infected rabbit acute epithelial keratitis models by Prof. James Hill at LSU Eye Center. LSU Medical Center, New Orleans, Louisiana. The unsacrified corneas will be inoculated with 25microl of a suspension of HSV-1 strain McKrae (Ixl0(5) Plaque Forming Unitslml. The lesions after infections and after topical dosing of 50 micro 1 solution of 1 mM derivative will be evaluated by Slit-Lamp Biomicroscopic Examination.
Funding Period: 1994-11-01 - 2001-11-30
more information: NIH RePORT

Top Publications

  1. ncbi Functional activity of a monocarboxylate transporter, MCT1, in the human retinal pigmented epithelium cell line, ARPE-19
    Soumyajit Majumdar
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, 5005 Rockhill Road, Kansas City, MO 64110, USA
    Mol Pharm 2:109-17. 2005
  2. ncbi Corneal absorption and anterior chamber pharmacokinetics of dipeptide monoester prodrugs of ganciclovir (GCV): in vivo comparative evaluation of these prodrugs with Val-GCV and GCV in rabbits
    Sriram Gunda
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64110-2499, USA
    J Ocul Pharmacol Ther 22:465-76. 2006
  3. ncbi Effect of lactide/glycolide ratio on the in vitro release of ganciclovir and its lipophilic prodrug (GCV-monobutyrate) from PLGA microspheres
    Kumar G Janoria
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, 5005 Rockhill Road, KPB, Kansas City, MO 64110 2499, USA
    Int J Pharm 338:133-41. 2007
  4. ncbi Controlled delivery of ganciclovir to the retina with drug-loaded Poly(d,L-lactide-co-glycolide) (PLGA) microspheres dispersed in PLGA-PEG-PLGA Gel: a novel intravitreal delivery system for the treatment of cytomegalovirus retinitis
    Sridhar Duvvuri
    Bioanalytical R and D, Wyeth Research, Pearl River, NY
    J Ocul Pharmacol Ther 23:264-74. 2007
  5. ncbi Novel approaches to retinal drug delivery
    Kumar G Janoria
    University of Missouri Kansas City, Department of Pharmaceutical Sciences, School of Pharmacy, 5005 Rockhill Road, Kansas City, MO 64110, USA
    Expert Opin Drug Deliv 4:371-88. 2007
  6. ncbi Functional activity of a large neutral amino acid transporter (LAT) in rabbit retina: a study involving the in vivo retinal uptake and vitreal pharmacokinetics of L-phenyl alanine
    Harisha Atluri
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, 5005 Rockhill Road, Kansas City, MO 64110 2499, USA
    Int J Pharm 347:23-30. 2008
  7. ncbi Dipeptide monoester ganciclovir prodrugs for transscleral drug delivery: targeting the oligopeptide transporter on rabbit retina
    Viral Kansara
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, Kansas City, MO, USA
    J Ocul Pharmacol Ther 23:321-34. 2007
  8. ncbi MDR- and CYP3A4-mediated drug-drug interactions
    Dhananjay Pal
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 5005 Rockhill Road, Kansas City, MO 64110-2499, USA
    J Neuroimmune Pharmacol 1:323-39. 2006
  9. ncbi Folic acid transport via high affinity carrier-mediated system in human retinoblastoma cells
    Viral Kansara
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, 5005 Rockhill Road, Kansas City, MO 64110 2499, USA
    Int J Pharm 355:210-9. 2008
  10. ncbi Ocular pharmacokinetics of acyclovir amino acid ester prodrugs in the anterior chamber: evaluation of their utility in treating ocular HSV infections
    Suresh Katragadda
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, Kansas City, MO, United States
    Int J Pharm 359:15-24. 2008

Detail Information

Publications37

  1. ncbi Functional activity of a monocarboxylate transporter, MCT1, in the human retinal pigmented epithelium cell line, ARPE-19
    Soumyajit Majumdar
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, 5005 Rockhill Road, Kansas City, MO 64110, USA
    Mol Pharm 2:109-17. 2005
    ..This cell line may thus be used as an effective screening tool for intravitreally administered drugs/prodrugs targeted toward MCT1 expressed on the RPE...
  2. ncbi Corneal absorption and anterior chamber pharmacokinetics of dipeptide monoester prodrugs of ganciclovir (GCV): in vivo comparative evaluation of these prodrugs with Val-GCV and GCV in rabbits
    Sriram Gunda
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64110-2499, USA
    J Ocul Pharmacol Ther 22:465-76. 2006
    ..Such facilitated absorption of prodrugs may be a result of a combination of transcellular passive diffusion and peptide transporter (PEPT1)-mediated transport across the corneal epithelium...
  3. ncbi Effect of lactide/glycolide ratio on the in vitro release of ganciclovir and its lipophilic prodrug (GCV-monobutyrate) from PLGA microspheres
    Kumar G Janoria
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, 5005 Rockhill Road, KPB, Kansas City, MO 64110 2499, USA
    Int J Pharm 338:133-41. 2007
    ....
  4. ncbi Controlled delivery of ganciclovir to the retina with drug-loaded Poly(d,L-lactide-co-glycolide) (PLGA) microspheres dispersed in PLGA-PEG-PLGA Gel: a novel intravitreal delivery system for the treatment of cytomegalovirus retinitis
    Sridhar Duvvuri
    Bioanalytical R and D, Wyeth Research, Pearl River, NY
    J Ocul Pharmacol Ther 23:264-74. 2007
    ....
  5. ncbi Novel approaches to retinal drug delivery
    Kumar G Janoria
    University of Missouri Kansas City, Department of Pharmaceutical Sciences, School of Pharmacy, 5005 Rockhill Road, Kansas City, MO 64110, USA
    Expert Opin Drug Deliv 4:371-88. 2007
    ..In this review article, the authors discuss various drug delivery strategies, devices and challenges associated with drug delivery to the retina...
  6. ncbi Functional activity of a large neutral amino acid transporter (LAT) in rabbit retina: a study involving the in vivo retinal uptake and vitreal pharmacokinetics of L-phenyl alanine
    Harisha Atluri
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, 5005 Rockhill Road, Kansas City, MO 64110 2499, USA
    Int J Pharm 347:23-30. 2008
    ..The purpose of this study is to elucidate the functional activity of large neutral amino acid transporter (LAT) in rabbit retina and to delineate its role in the retinal uptake and intravitreal pharmacokinetics of L-phenylalanine (L-Phe)...
  7. ncbi Dipeptide monoester ganciclovir prodrugs for transscleral drug delivery: targeting the oligopeptide transporter on rabbit retina
    Viral Kansara
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, Kansas City, MO, USA
    J Ocul Pharmacol Ther 23:321-34. 2007
    ..The overall aim of this research work was to evaluate a series of dipeptide monoester prodrugs of an antiviral agent, ganciclovir (GCV), for oligopeptide transporter-targeted transscleral drug delivery to rabbit retina...
  8. ncbi MDR- and CYP3A4-mediated drug-drug interactions
    Dhananjay Pal
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 5005 Rockhill Road, Kansas City, MO 64110-2499, USA
    J Neuroimmune Pharmacol 1:323-39. 2006
    ..This article provides an insight into low and variable oral bioavailability and related complications leading to loss of therapeutic activity of MDR and CYP 450 substrates...
  9. ncbi Folic acid transport via high affinity carrier-mediated system in human retinoblastoma cells
    Viral Kansara
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, 5005 Rockhill Road, Kansas City, MO 64110 2499, USA
    Int J Pharm 355:210-9. 2008
    ..This research work demonstrated, for the first time, the functional and molecular existence of a specialized high affinity carrier-mediated system for folic acid uptake, in human retinoblastoma cells...
  10. ncbi Ocular pharmacokinetics of acyclovir amino acid ester prodrugs in the anterior chamber: evaluation of their utility in treating ocular HSV infections
    Suresh Katragadda
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, Kansas City, MO, United States
    Int J Pharm 359:15-24. 2008
    ..To evaluate in vivo corneal absorption of the amino acid prodrugs of acyclovir (ACV) using a topical well model and microdialysis in rabbits...
  11. ncbi Synthesis, metabolism and cellular permeability of enzymatically stable dipeptide prodrugs of acyclovir
    Ravi S Talluri
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, 5005 Rockhill Road Kansas City, Missouri 64110 2499, USA
    Int J Pharm 361:118-24. 2008
    ..This strategy improved both the cellular permeability and the amount of intact prodrug transported which would enable targeting the nutrient transporters at blood ocular barrier (BOB)...
  12. ncbi Pharmacokinetics of amino acid ester prodrugs of acyclovir after oral administration: interaction with the transporters on Caco-2 cells
    Suresh Katragadda
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, 5005 Rockhill Road, Kansas City, MO 64110 2499, USA
    Int J Pharm 362:93-101. 2008
    ..The amino acid ester prodrug SACV owing to its enhanced stability, higher AUC and better concentration at last time point seems to be a promising candidate for the oral treatment of herpes infections...
  13. ncbi Recent perspectives in ocular drug delivery
    Ripal Gaudana
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, 5005 Rockhill Road, Kansas City, Missouri 64110 2499, USA
    Pharm Res 26:1197-216. 2009
    ..Current momentum in the invention of new drug delivery systems hold a promise towards much improved therapies for the treatment of vision threatening disorders...
  14. ncbi Enhanced corneal absorption of erythromycin by modulating P-glycoprotein and MRP mediated efflux with corticosteroids
    Sudharshan Hariharan
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, 5005 Rockhill Road, Kansas City, MO 64110, USA
    Pharm Res 26:1270-82. 2009
    ..The objectives were (i) to test in vivo functional activity of MRP2 on rabbit corneal epithelium and (ii) to evaluate modulation of P-gp and MRP2 mediated efflux of erythromycin when co-administered with corticosteroids...
  15. ncbi Recent patents and advances in ophthalmic drug delivery
    Kumar G Janoria
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, Kansas City, MO 64110 2499, USA
    Recent Pat Drug Deliv Formul 1:161-70. 2007
    ..As a whole, this article is intended to provide a valuable insight into current trends in the field of ocular drug delivery and highlights advances made in patent literature...
  16. ncbi Molecular expression and functional evidence of a drug efflux pump (BCRP) in human corneal epithelial cells
    Pradeep K Karla
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, Kansas City, Missouri 64110 2499, USA
    Curr Eye Res 34:1-9. 2009
    ..The objective of this study was to explore physical barriers for ocular drug absorption and to verify the presence and possible role of BCRP as a barrier for ocular drug resistance...
  17. ncbi Vitreal pharmacokinetics of biotinylated ganciclovir: role of sodium-dependent multivitamin transporter expressed on retina
    Kumar G Janoria
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, Kansas City, Missouri 64110 2499, USA
    J Ocul Pharmacol Ther 25:39-49. 2009
    ..Study also aims to delineate the vitreal pharmacokinetics of biotin-GCV...
  18. ncbi Molecular evidence and functional expression of a novel drug efflux pump (ABCC2) in human corneal epithelium and rabbit cornea and its role in ocular drug efflux
    Pradeep K Karla
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri, Kansas City, MO 64110, United States
    Int J Pharm 336:12-21. 2007
    ..A-->B transport of [(3)H]-cyclosporine-A was elevated in the presence of MK-571 in freshly excised rabbit cornea indicating potential role of this efflux transporter and high clinical significance of this finding...
  19. ncbi Functional characterization of peptide transporters in MDCKII-MDR1 cell line as a model for oral absorption studies
    Sheetal Agarwal
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, 5005 Rockhill Road, Kansas City, MO 64110 2499, USA
    Int J Pharm 332:147-52. 2007
    ..Results from these studies suggest the application of MDCKII-MDR1 cell line as a rapid effective tool to study peptide mediated influx of compounds that may be substrates for both P-gp and peptide transporters...
  20. ncbi Molecular evidence and functional expression of multidrug resistance associated protein (MRP) in rabbit corneal epithelial cells
    Pradeep K Karla
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, 5005 Rockhill Road, Kansas City, MO 64110 2499, USA
    Exp Eye Res 84:53-60. 2007
    ..For the first time we have demonstrated high expression of MRP-2 in rabbit corneal epithelium and its functional activity causing drug efflux. RT-PCR, immunoprecipitation followed by Western blot analysis further confirms the result...
  21. ncbi Identification and functional characterization of riboflavin transporter in human-derived retinoblastoma cell line (Y-79): mechanisms of cellular uptake and translocation
    Viral Kansara
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, Kansas City, MO 64112-2499, USA
    J Ocul Pharmacol Ther 21:275-87. 2005
    ....
  22. ncbi Development of a novel formulation containing poly(d,l-lactide-co-glycolide) microspheres dispersed in PLGA-PEG-PLGA gel for sustained delivery of ganciclovir
    Sridhar Duvvuri
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 5005, Rockhill Road, Kansas City, MO 64110, USA
    J Control Release 108:282-93. 2005
    ..In conclusion, this study reports the development of PLGA microspheres with high payloads and their PLGA-PEG-PLGA gel based formulations. Drug release equations have been developed that effectively describe the triphasic GCV release...
  23. ncbi Synthesis, physicochemical properties and antiviral activities of ester prodrugs of ganciclovir
    Kunal Patel
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 5005 Rockhill Road, Kansas City, MO 64110-2499, USA
    Int J Pharm 305:75-89. 2005
    ..In conclusion, the diester GCV prodrugs demonstrated excellent chemical stability, high aqueous solubility and markedly enhanced antiviral potency against the herpes viruses without any increase in cytotoxicity...
  24. ncbi Microdialysis assessment of drug delivery systems for vitreoretinal targets
    Sridhar Duvvuri
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64110, USA
    Adv Drug Deliv Rev 57:2080-91. 2005
    ..Special problems examined include anterior and posterior ocular clearance mechanisms, intraocular metabolism and active transport of drugs...
  25. ncbi Identification and characterization of a Na+-dependent neutral amino acid transporter, ASCT1, in rabbit corneal epithelial cell culture and rabbit cornea
    Suresh Katragadda
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri 64110-2499, USA
    Curr Eye Res 30:989-1002. 2005
    ..CONCLUSIONS: L-Alanine, the chosen model substrate, was actively transported by Na+-dependent, neutral amino acid exchanger ASCT1, which was identified and functionally characterized on rPCEC cells and rabbit cornea...
  26. ncbi Role of efflux pumps and metabolising enzymes in drug delivery
    Suresh Katragadda
    University of Missouri-Kansas City, Division of Pharmaceutical Sciences, School of Pharmacy, 64110-2499, USA
    Expert Opin Drug Deliv 2:683-705. 2005
    ..In summary, this review emphasises the urgent need to make changes in drug discovery and drug delivery as efflux pumps and metabolising enzymes play an important role in drug delivery and disposition...
  27. ncbi Effect of polymer blending on the release of ganciclovir from PLGA microspheres
    Sridhar Duvvuri
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 5005, Rockhill Road, Kansas City, Missouri 64110, USA
    Pharm Res 23:215-23. 2006
    ..Polymer blending can effectively alter drug-release rates of controlled delivery systems in the absence of any additives...
  28. ncbi Dipeptide monoester ganciclovir prodrugs for treating HSV-1-induced corneal epithelial and stromal keratitis: in vitro and in vivo evaluations
    Soumyajit Majumdar
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 5005 Rockhill Road, 64110-2499, USA
    J Ocul Pharmacol Ther 21:463-74. 2005
    ..CONCLUSIONS: Val-Val-GCV demonstrates excellent corneal permeability and chemical stability, high aqueous solubility, and substantial in vivo antiviral activity against the HSV-1...
  29. ncbi Biotin uptake and cellular translocation in human derived retinoblastoma cell line (Y-79): a role of hSMVT system
    Viral Kansara
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, 5005 Rockhill Road, Kansas City, MO 64110-2499, USA
    Int J Pharm 312:43-52. 2006
    ..These studies demonstrated for the first time the existence of a human sodium dependant multivitamin transporter (hSMVT), a specialized carrier-mediated system for biotin uptake, in human derived retinoblastoma cells...
  30. ncbi Simultaneous modulation of transport and metabolism of acyclovir prodrugs across rabbit cornea: An approach involving enzyme inhibitors
    Suresh Katragadda
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 5005 Rockhill Road, Kansas City, MO 64110-2499, USA
    Int J Pharm 320:104-13. 2006
    ..In conclusion, utility of enzyme inhibitors to modulate transport and metabolism of prodrugs appears to be promising strategy for enhancing drug transport across cornea...
  31. ncbi Modulation of P-glycoprotein-mediated efflux by prodrug derivatization: an approach involving peptide transporter-mediated influx across rabbit cornea
    Suresh Katragadda
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri, USA
    J Ocul Pharmacol Ther 22:110-20. 2006
    ..Enhanced permeabilities of the prodrugs indicate that drug derivatization can be a viable strategy for overcoming P-gp-mediated efflux...
  32. ncbi Mechanism of L-ascorbic acid uptake by rabbit corneal epithelial cells: evidence for the involvement of sodium-dependent vitamin C transporter 2
    Ravi S Talluri
    School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri 64110, USA
    Curr Eye Res 31:481-9. 2006
    ..A saturable, sodium dependent, and pH sensitive transporter with high specificity for L-ascorbic acid was functionally characterized and was identified as SVCT2...
  33. ncbi In vivo ocular pharmacokinetics of acyclovir dipeptide ester prodrugs by microdialysis in rabbits
    Banmeet S Anand
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri 64110, USA
    Mol Pharm 3:431-40. 2006
    ..The dipeptide prodrug GVACV owing to its enhanced absorption of ACV seems to be a promising candidate for the treatment of ocular HSV infections...
  34. ncbi Vitreal pharmacokinetics of dipeptide monoester prodrugs of ganciclovir
    Soumyajit Majumdar
    Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, Oxford, MS, USA
    J Ocul Pharmacol Ther 22:231-41. 2006
    ..CONCLUSIONS: Considering retinal GCV concentrations generated and vitreal pharmacokinetic profiles, Gly-Val-GCV appears to be a lead candidate for further in vivo evaluation against human cytomegalovirus (HCMV) retinitis...
  35. ncbi Biotin uptake by rabbit corneal epithelial cells: role of sodium-dependent multivitamin transporter (SMVT)
    Kumar G Janoria
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri 64110-2499, USA
    Curr Eye Res 31:797-809. 2006
    ..Further, the presence of biotin in tears suggests the physiological significance of this transporter in rabbit corneal epithelium...
  36. ncbi Identification and functional expression of a carrier-mediated riboflavin transport system on rabbit corneal epithelium
    Sudharshan Hariharan
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri 64112-2499, USA
    Curr Eye Res 31:811-24. 2006
    ....
  37. ncbi Interaction of ocular hypotensive agents (PGF2 alpha analogs-bimatoprost, latanoprost, and travoprost) with MDR efflux pumps on the rabbit cornea
    Sudharshan Hariharan
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, Kansas City, Missouri 64110, USA
    J Ocul Pharmacol Ther 25:487-98. 2009
    ....