title: Pharmacokinetics and posterior segment biodistribution of ESBA105, an anti-TNF-alpha single-chain antibody, upon topical administration to the rabbit eye.
abstract: OBJECTIVE
  The purpose of this study was to characterize local distribution and systemic absorption of the tumor necrosis factor (TNF)-alpha inhibitory single-chain antibody fragment (scFv) ESBA105 following topical administration to the eye in vivo.
  
  
  METHODS
  Rabbits received ESBA105 as topical eye drops in two dosing regimens. First, pharmacokinetics after the topical route of administration was compared to the intravenous (i.v.) route by means of applying the identical cumulative daily dose of ESBA105. In a second study rabbits received five eye drops daily for six consecutive days in a lower frequency topical dosing regimen. Kinetics and biodistribution of ESBA105 in ocular tissues and fluids as well as in sera were determined in all animals.
  
  
  RESULTS
  After topical administration to the eye, ESBA105 quickly reaches therapeutic concentrations in all ocular compartments. Systemic exposure after topical administration is 25,000-fold lower than exposure after i.v. injection of the identical cumulative daily dose. ESBA105 levels in vitreous humor and neuroretina are significantly higher on topical administration than after i.v. injection. Absolute and relative intraocular biodistribution of ESBA105 is different with topical and systemic delivery routes. Compared to its terminal half-life in circulation (7 hours), the vitreal half-life of ESBA105 is significantly enhanced (16-24 hours).
  
  
  CONCLUSIONS
  On topical administration, ESBA105 is efficiently absorbed and distributed to all compartments of the eye, whereby systemic drug exposure is very low. Based on its unique intraocular biodistribution and pharmacokinetics and the absolute intraocular levels reached, topical ESBA105 appears highly attractive for treatment of various ophthalmological disorders.
authors.affiliation: ESBATech AG, Schlieren, Switzerland.
authors.forename: Esther
authors.initials: E
authors.lastname: Furrer
authors.forename: Marianne
authors.initials: M
authors.lastname: Berdugo
authors.forename: Cinzia
authors.initials: C
authors.lastname: Stella
authors.forename: Francine
authors.initials: F
authors.lastname: Behar-Cohen
authors.forename: Robert
authors.initials: R
authors.lastname: Gurny
authors.forename: Ulrich
authors.initials: U
authors.lastname: Feige
authors.forename: Peter
authors.initials: P
authors.lastname: Lichtlen
authors.forename: David M
authors.initials: DM
authors.lastname: Urech