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In vivo ocular pharmacokinetics of acyclovir dipeptide ester prodrugs by microdialysis in rabbits.
Mol Pharm 2006 Jul-Aug; 3(4):431-40MP

Abstract

In vivo corneal absorption of the dipeptide prodrugs of acyclovir (ACV) was evaluated using microdialysis in rabbits. A corneal well was placed on the cornea of the anesthetized New Zealand White rabbits with implanted linear probes into the aqueous humor. Two hundred microliters of a 1% solution of L-valine-ACV (VACV), glycine-valine-ACV (GVACV), valine-valine-ACV (VVACV), and valine-tyrosine-ACV (VYACV) was placed in the corneal well and was allowed to diffuse for a period of 2 h, following which the drug solution was aspirated and well removed. Samples were collected every 20 min throughout the infusion and postinfusion phases and were analyzed by HPLC to obtain the aqueous humor concentrations. Absorption rate constants of all the compounds were found to be lower than the elimination rate constants. GVACV exhibited highest absorption rate (ka) compared with other prodrugs, but all the prodrugs showed similar terminal elimination rate (lambda(z)). The time of maximum absorption (Tmax) of ACV after administration of VACV and the dipeptide prodrugs did not vary significantly (p < 0.05). GVACV exhibited the highest concentration (Cmax) and area under curve (AUC) upon absorption (p < 0.05) compared to VACV, VVACV, and VYACV. Dipeptide prodrugs of ACV were absorbed through the cornea at similar rates but to varying extents. The dipeptide prodrug GVACV owing to its enhanced absorption of ACV seems to be a promising candidate for the treatment of ocular HSV infections.

Authors+Show Affiliations

Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri 64110, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16889437

Citation

Anand, Banmeet S., et al. "In Vivo Ocular Pharmacokinetics of Acyclovir Dipeptide Ester Prodrugs By Microdialysis in Rabbits." Molecular Pharmaceutics, vol. 3, no. 4, 2006, pp. 431-40.
Anand BS, Katragadda S, Gunda S, et al. In vivo ocular pharmacokinetics of acyclovir dipeptide ester prodrugs by microdialysis in rabbits. Mol Pharm. 2006;3(4):431-40.
Anand, B. S., Katragadda, S., Gunda, S., & Mitra, A. K. (2006). In vivo ocular pharmacokinetics of acyclovir dipeptide ester prodrugs by microdialysis in rabbits. Molecular Pharmaceutics, 3(4), pp. 431-40.
Anand BS, et al. In Vivo Ocular Pharmacokinetics of Acyclovir Dipeptide Ester Prodrugs By Microdialysis in Rabbits. Mol Pharm. 2006;3(4):431-40. PubMed PMID: 16889437.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo ocular pharmacokinetics of acyclovir dipeptide ester prodrugs by microdialysis in rabbits. AU - Anand,Banmeet S, AU - Katragadda,Suresh, AU - Gunda,Sriram, AU - Mitra,Ashim K, PY - 2006/8/8/pubmed PY - 2006/10/18/medline PY - 2006/8/8/entrez SP - 431 EP - 40 JF - Molecular pharmaceutics JO - Mol. Pharm. VL - 3 IS - 4 N2 - In vivo corneal absorption of the dipeptide prodrugs of acyclovir (ACV) was evaluated using microdialysis in rabbits. A corneal well was placed on the cornea of the anesthetized New Zealand White rabbits with implanted linear probes into the aqueous humor. Two hundred microliters of a 1% solution of L-valine-ACV (VACV), glycine-valine-ACV (GVACV), valine-valine-ACV (VVACV), and valine-tyrosine-ACV (VYACV) was placed in the corneal well and was allowed to diffuse for a period of 2 h, following which the drug solution was aspirated and well removed. Samples were collected every 20 min throughout the infusion and postinfusion phases and were analyzed by HPLC to obtain the aqueous humor concentrations. Absorption rate constants of all the compounds were found to be lower than the elimination rate constants. GVACV exhibited highest absorption rate (ka) compared with other prodrugs, but all the prodrugs showed similar terminal elimination rate (lambda(z)). The time of maximum absorption (Tmax) of ACV after administration of VACV and the dipeptide prodrugs did not vary significantly (p < 0.05). GVACV exhibited the highest concentration (Cmax) and area under curve (AUC) upon absorption (p < 0.05) compared to VACV, VVACV, and VYACV. Dipeptide prodrugs of ACV were absorbed through the cornea at similar rates but to varying extents. The dipeptide prodrug GVACV owing to its enhanced absorption of ACV seems to be a promising candidate for the treatment of ocular HSV infections. SN - 1543-8384 UR - https://www.unboundmedicine.com/medline/citation/16889437/In_vivo_ocular_pharmacokinetics_of_acyclovir_dipeptide_ester_prodrugs_by_microdialysis_in_rabbits_ L2 - https://dx.doi.org/10.1021/mp0498998 DB - PRIME DP - Unbound Medicine ER -