Intravitreal and plasma cidofovir concentrations after intravitreal and intravenous administration in AIDS patients with cytomegalovirus retinitis

J Ocul Pharmacol Ther. 1998 Apr;14(2):147-51. doi: 10.1089/jop.1998.14.147.

Abstract

This study was undertaken to evaluate the intravitreal and plasma concentrations of cidofovir (HPMPC) after intravitreal and intravenous administration in AIDS patients with cytomegalovirus retinitis. Cohort series; undiluted vitreous and blood were collected from 9 patients at the time of pars plana vitrectomy. Vitreous samples from 9 eyes of 9 patients and plasma samples from 4 patients were assayed with high-performance liquid chromatography to determine cidofovir levels. The only eye that had a detectable vitreous concentration (673.7 ng/ml) was injected with 20 microg 24 hours prior to the surgery. The remaining samples including plasma were below the detection point of the assay (100 ng/ml) and were injected between 5 and 40 days prior to sampling. The intravitreal concentration of cidofovir in humans is consistent with pharmacokinetics data in laboratory animals, and suggests that the long duration of antiviral effect (1-3 months) in clinical trials is due to a prolonged intracellular half-life in retinal tissue.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acquired Immunodeficiency Syndrome / complications*
  • Adult
  • Antiviral Agents / blood*
  • Antiviral Agents / pharmacokinetics*
  • Antiviral Agents / therapeutic use
  • Cidofovir
  • Cohort Studies
  • Cytomegalovirus Infections / complications*
  • Cytomegalovirus Infections / drug therapy*
  • Cytosine / analogs & derivatives*
  • Cytosine / blood
  • Cytosine / pharmacokinetics
  • Cytosine / therapeutic use
  • Humans
  • Injections
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Organophosphonates*
  • Organophosphorus Compounds / blood*
  • Organophosphorus Compounds / pharmacokinetics*
  • Organophosphorus Compounds / therapeutic use
  • Osmolar Concentration
  • Prospective Studies
  • Retinitis / virology*
  • Vitreous Body / metabolism*

Substances

  • Antiviral Agents
  • Organophosphonates
  • Organophosphorus Compounds
  • Cytosine
  • Cidofovir