title: Effect of partial retinal destruction and gliosis on the intravitreal pharmacokinetics of HPMPC.
abstract: OBJECTIVE
  Intravitreal HPMPC ([S]-1-[3-hydroxy-2 phosphonylmethoxypropyl cytosine) has a long antiviral effect in patients with cytomegalovirus retinitis. The authors evaluated the pharmacokinetics of intravitreal injections of HPMPC to understand major route of HPMPC elimination in a pigmented rabbit that had undergone scatter laser photocoagulation over half of the retinal surface.
  
  
  METHODS
  The authors treated the inferior half of the retina, receiving an average of 605 grade 3 or 4 (gray-white or white) diode laser burns in a scatter fashion in the left eyes of 13 rabbits. After 4 weeks, 13 rabbits received intravitreal injection of HPMPC (100 micrograms in 0.1 mL) in both eyes. Forty-eight hours after injection, unfixed vitreous samples were obtained for high-pressure liquid chromatography analysis. Two rabbits were used for light microscopic examination of diode laser photocoagulated retina with the perfusion fixation.
  
  
  RESULTS
  The HPMPC concentration in the vitreous was 5.93 +/- 1.75 micrograms/mL in the laser-treated group and 4.76 +/- 1.2 micrograms/mL in the control group 48 hours after intravitreal HPMPC injection. The difference was statistically different (P = 0.037).
  
  
  CONCLUSIONS
  Results showed a higher concentration of intravitreal HPMPC in the eye that had approximately 25% of the retina destroyed by the laser photocoagulation. The higher concentration is likely the result of reduced elimination and a concomitant increase in half-life. This suggests that HPMPC may be eliminated via the retinal route. Eyes with more extensive retinal involvement with human cytomegalovirus may have an even longer duration of action of intravitreal HPMPC. This may lead to modification of dosing regimens.
authors: Department of Ophthalmology, University of California-San Diego School of Medicine, USA.
authors: J W
authors: JW
authors: Kim
authors: W
authors: W
authors: el-Haig
authors: E V
authors: EV
authors: Capparelli
authors: G
authors: G
authors: Besen
authors: J D
authors: JD
authors: Connor
authors: W R
authors: WR
authors: Freeman
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005911:Gliosis / Q000209:etiology*; D006207:Half-Life; D007267:Injections; D017075:Laser Coagulation / Q000009:adverse effects; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics*; D011817:Rabbits; D012160:Retina / Q000601:surgery*; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir