Microdialysis for Vitreal Pharmacokinetics

  • Ravi D. Vaishya
  • Hari Krishna Ananthula
  • Ashim K. Mitra
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 2)


Microdialysis has been an instrumental sampling technique to study ocular pharmacokinetics without sacrificing a huge number of animals. It has undergone significant transformations in the last decade and several animal models have been established for sampling inaccessible posterior segment tissues such as vitreous humor. Remarkable progress has been made in the probe design and validation techniques. In the following chapter we have discussed the principle and development of various animal models related to posterior segments.


Aqueous Humor Diabetic Macular Edema Posterior Segment Vitreous Humor Blood Retinal Barrier 
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Poly(dl-lactide-co-glycolide)-poly(ethylene glycol)-poly(dl-lactide-co-glycolide)







Supported by National Institutes of Health grants R01EY 09171–16 and R01EY 10659–14.


  1. Adachi A, Hasegawa M, Ebihara S (1995) Measurement of circadian rhythms of ocular melatonin in the pigeon by in vivo microdialysis. Neuroreport 7:286–288PubMedGoogle Scholar
  2. Adachi A, Nogi T, Ebihara S (1998) Phase-relationship and mutual effects between circadian rhythms of ocular melatonin and dopamine in the pigeon. Brain Res 792:361–369PubMedCrossRefGoogle Scholar
  3. Amberg G, Lindefors N (1989) Intracerebral microdialysis: II. Mathematical studies of diffusion kinetics. J Pharmacol Methods 22:157–183PubMedCrossRefGoogle Scholar
  4. Anand BS, Atluri H, Mitra AK (2004) Validation of an ocular microdialysis technique in rabbits with permanently implanted vitreous probes: systemic and intravitreal pharmacokinetics of fluorescein. Int J Pharm 281:79–88PubMedCrossRefGoogle Scholar
  5. Atluri H, Mitra AK (2003) Disposition of short-chain aliphatic alcohols in rabbit vitreous by ocular microdialysis. Exp Eye Res 76:315–320PubMedCrossRefGoogle Scholar
  6. Atluri H, Talluri RS, Mitra AK (2008) 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. Int J Pharm 347:23–30PubMedCrossRefGoogle Scholar
  7. Ben-Nun J, Cooper RL, Cringle SJ, Constable IJ (1988) Ocular dialysis. A new technique for in vivo intraocular pharmacokinetic measurements. Arch Ophthalmol 106:254–259PubMedGoogle Scholar
  8. Dias CS, Mitra AK (2003) Posterior segment ocular pharmacokinetics using microdialysis in a conscious rabbit model. Invest Ophthalmol Vis Sci 44:300–305PubMedCrossRefGoogle Scholar
  9. Duvvuri S, Gandhi MD, Mitra AK (2003) Effect of p-glycoprotein on the ocular disposition of a model substrate, quinidine. Curr Eye Res 27:345–353PubMedCrossRefGoogle Scholar
  10. Duvvuri S, Janoria KG, Pal D, Mitra AK (2007) 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. J Ocul Pharmacol Ther 23:264–274PubMedCrossRefGoogle Scholar
  11. Ebihara S, Adachi A, Hasegawa M, Nogi T, Yoshimura T, Hirunagi K (1997) In vivo microdialysis studies of pineal and ocular melatonin rhythms in birds. Biol Signals 6:233–240PubMedCrossRefGoogle Scholar
  12. Gunnarson G, Jakobsson AK, Hamberger A, Sjostrand J (1987) Free amino acids in the pre-retinal vitreous space. Effect of high potassium and nipecotic acid. Exp Eye Res 44:235–244PubMedCrossRefGoogle Scholar
  13. Hosoya K, Makihara A, Tsujikawa Y, Yoneyama D, Mori S, Terasaki T, Akanuma S, Tomi M, Tachikawa M (2009) Roles of inner blood-retinal barrier organic anion transporter 3 in the vitreous/retina-to-blood efflux transport of p-aminohippuric acid, benzylpenicillin, and 6-mercaptopurine. J Pharmacol Exp Ther 329:87–93PubMedCrossRefGoogle Scholar
  14. Hughes PM, Krishnamoorthy R, Mitra AK (1996) Vitreous disposition of two acycloguanosine antivirals in the albino and pigmented rabbit models: a novel ocular microdialysis technique. J Ocul Pharmacol Ther 12:209–224PubMedCrossRefGoogle Scholar
  15. Janoria KG, Boddu SH, Wang Z, Paturi DK, Samanta S, Pal D, Mitra AK (2009) Vitreal pharmacokinetics of biotinylated ganciclovir: role of sodium-dependent multivitamin transporter expressed on retina. J Ocul Pharmacol Ther 25:39–49PubMedCrossRefGoogle Scholar
  16. Kalant H (1958) A microdialysis procedure for extraction and isolation of corticosteroids from peripheral blood plasma. Biochem J 69:99–103PubMedGoogle Scholar
  17. Katayama K, Ohshima Y, Tomi M, Hosoya K (2006) Application of microdialysis to evaluate the efflux transport of estradiol 17-beta glucuronide across the rat blood-retinal barrier. J Neurosci Methods 156:249–256PubMedCrossRefGoogle Scholar
  18. Louzada-Junior P, Dias JJ, Santos WF, Lachat JJ, Bradford HF, Coutinho-Netto J (1992) Glutamate release in experimental ischaemia of the retina: an approach using microdialysis. J Neurochem 59:358–363PubMedCrossRefGoogle Scholar
  19. Macha S, Mitra AK (2001) Ocular pharmacokinetics in rabbits using a novel dual probe microdialysis technique. Exp Eye Res 72:289–299PubMedCrossRefGoogle Scholar
  20. Majumdar S, Kansara V, Mitra AK (2006) Vitreal pharmacokinetics of dipeptide monoester prodrugs of ganciclovir. J Ocul Pharmacol Ther 22:231–241PubMedCrossRefGoogle Scholar
  21. Maurice DM (1957) The exchange of sodium between the vitreous body and the blood and aqueous humour. J Physiol 137:110–125PubMedGoogle Scholar
  22. Maurice DM (1959) Protein dynamics in the eye studied with labelled proteins. Am J Ophthalmol 47:361–368PubMedGoogle Scholar
  23. Pow DV (2001) Amino acids and their transporters in the retina. Neurochem Int 38:463–484PubMedCrossRefGoogle Scholar
  24. Puppala D, Maaswinkel H, Mason B, Legan SJ, Li L (2004) An in vivo microdialysis study of light/dark-modulation of vitreal dopamine release in zebrafish. J Neurocytol 33:193–201PubMedCrossRefGoogle Scholar
  25. Rittenhouse KD, Pollack GM (2000) Microdialysis and drug delivery to the eye. Adv Drug Deliv Rev 45:229–241PubMedCrossRefGoogle Scholar
  26. Sen HA, Berkowitz BA, Ando N, de Juan E Jr (1992) In vivo imaging of breakdown of the inner and outer blood-retinal barriers. Invest Ophthalmol Vis Sci 33:3507–3512PubMedGoogle Scholar
  27. Stempels N, Tassignon MJ, Sarre S, Nguyen-Legros J (1994) Microdialysis measurement of catecholamines in rabbit vitreous after retinal laser photocoagulation. Exp Eye Res 59:433–439PubMedCrossRefGoogle Scholar
  28. Tagami M, Kusuhara S, Honda S, Tsukahara Y, Negi A (2009) Expression of ATP-binding cassette transporters at the inner blood-retinal barrier in a neonatal mouse model of oxygen-induced retinopathy. Brain Res 1283:186–193PubMedCrossRefGoogle Scholar
  29. Ungerstedt U, Pycock C (1974) Functional correlates of dopamine neurotransmission. Bull Schweiz Akad Med Wiss 30:44–55PubMedGoogle Scholar
  30. Waga J, Ehinger B (1995) Passage of drugs through different intraocular microdialysis membranes. Graefes Arch Clin Exp Ophthalmol 233:31–37PubMedCrossRefGoogle Scholar
  31. Waga J, Ohta A, Ehinger B (1991) Intraocular microdialysis with permanently implanted probes in rabbit. Acta Ophthalmol (Copenh) 69:618–624CrossRefGoogle Scholar
  32. Waga J, Nilsson-Ehle I, Ljungberg B, Skarin A, Stahle L, Ehinger B (1999) Microdialysis for pharmacokinetic studies of ceftazidime in rabbit vitreous. J Ocul Pharmacol Ther 15:455–463PubMedCrossRefGoogle Scholar
  33. Wages SA, Church WH, Justice JB Jr (1986) Sampling considerations for on-line microbore liquid chromatography of brain dialysate. Anal Chem 58:1649–1656PubMedCrossRefGoogle Scholar
  34. Wang Y, Wong SL, Sawchuk RJ (1993) Microdialysis calibration using retrodialysis and zero-net flux: application to a study of the distribution of zidovudine to rabbit cerebrospinal fluid and thalamus. Pharm Res 10:1411–1419PubMedCrossRefGoogle Scholar
  35. Yoneyama D, Shinozaki Y, Lu WL, Tomi M, Tachikawa M, Hosoya K (2010) Involvement of system A in the retina-to-blood transport of l-proline across the inner blood-retinal barrier. Exp Eye Res 90:507–513PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2011

Authors and Affiliations

  • Ravi D. Vaishya
    • 1
  • Hari Krishna Ananthula
    • 1
  • Ashim K. Mitra
    • 2
  1. 1.Division of Pharmaceutical SciencesUniversity of Missouri-Kansas City, School of PharmacyKansas CityUSA
  2. 2.Division of Pharmaceutical SciencesUniversity of Missouri-Kansas City, School of PharmacyKansas CityUSA

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