title: Vitreous pharmacokinetics and bioavailability of memantine after subtenon, intravenous, and intravitreal administration in rabbits.
abstract: OBJECTIVE
  This study evaluated the vitreous pharmacokinetics and vitreous bioavailability of memantine following posterior-subtenon administration (PST) compared to intravitreal (INT) and intravenous routes (INV) in rabbits.
  
  
  METHODS
  Vitreous pharmacokinetic analysis was performed on female New Zealand (NZ) albino rabbits after PST, INT, and INV administration and calculating the pharmacokinetic parameters that describe memantine vitreous distribution. The vitreous bioavailability (F) and the relative vitreous bioavailability of memantine was estimated after posterior-subtenon administration (Frel (pst/int)) and after intravenous route (Frel (inv/int)) compared with intravitreal administration. Relative vitreous bioavailability of memantine was also estimated following PST administration compared with vitreous concentrations after intravenous administration (Frel (pst/inv)).
  
  
  RESULTS
  Memantine kinetics in the vitreous of NZ albino rabbits after PST administration can be explained by a one-compartment model, which was characterized by a fast absorption process, and a short terminal half-life. Vitreous pharmacokinetics following INV administration was also characterized by a fast absorption process, a terminal half-life significantly longer than the subtenon route, and low area under the curve values. High vitreous bioavailability after PST was observed, and the relative vitreous bioavailability of memantine following PST administration (0.53%) was greater than for intravenous administration (0.02%).
  
  
  CONCLUSIONS
  Our results suggest that memantine reaches the vitreous after PST administration by local diffusion. These data also show that local diffusion of the drug is responsible for greater vitreous availability of memantine following PST administration compared with INV administration.
authors.affiliation: 1 Department of Ophthalmology, Miguel Servet University Hospital and Aragon Health Sciences Institute (I+CS), University of Zaragoza , Zaragoza, Spain .
authors.forename: Esther
authors.initials: E
authors.lastname: Prieto
authors.forename: Susana
authors.initials: S
authors.lastname: Pérez
authors.forename: Luis E
authors.initials: LE
authors.lastname: Pablo
authors.forename: Maria A
authors.initials: MA
authors.lastname: García
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Bregante
mesh_terms: D000818:Animals; D001682:Biological Availability; D005260:Female; D007275:Injections, Intravenous; D058449:Intravitreal Injections / Q000379:methods*; D008559:Memantine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011817:Rabbits; D014822:Vitreous Body / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D008559:Memantine