title: Equilibrium binding interactions between lotrafilcon a soft contact lenses and the two prostaglandin antiglaucoma drugs bimatoprost and tafluprost.
abstract: OBJECTIVE
  To determine the equilibrium binding constant (EB) values of bimatoprost and tafluprost drug product formulations in contact with lotrafilcon A soft contact lenses and to characterize the importance of drug molecule hydrophobicity in controlling the binding interactions.
  
  
  METHODS
  Bimatoprost Ophthalmic Solution and Tafluprost Ophthalmic Solution (Saflutan) were incubated with lotrafilcon A lens material for timed intervals at 25°C and 37°C. Aliquots were withdrawn, filtered, and tested using reverse-phase ultrahigh-performance liquid chromatography with respect to [bimatoprost] or [tafluprost] remaining in the solution. A series of homologous dialkyl phthalate esters and a series of homologous p-hydroxybenzoic acid alkyl esters were also tested as reference compounds.
  
  
  RESULTS
  Bimatoprost and tafluprost were rapidly (within 15 min) absorbed from the solution by lotrafilcon A lenses, reaching an equilibrium within 60 min. At any lens:solution (w/v) ratio, the extent of drug binding to lens material was greater for tafluprost than for bimatoprost. The log(EB) values correlated with solute octanol:water partition coefficient (logP) values, indicating that hydrophobic interactions are important in controlling solute partitioning into the lens material.
  
  
  CONCLUSIONS
  This study established the quantitative relationships between tafluprost and bimatoprost binding to lotrafilcon A lenses. The fraction of bimatoprost or tafluprost that binds to lotrafilcon A increases with increasing lens:solution (w/v) ratio. For a 60 µL dose volume applied to a single contact lens, 16% of initially present bimatoprost remains in the solution, whereas only 6% of initially present tafluprost remains in the solution. These calculations clearly demonstrate that both drugs partition extensively into lotrafilcon A contact lens material. Although the clinical implications of such binding can only be surmised, it would seem prudent to caution contact lens wearers to remove the lenses before administering either prostaglandin drug.
authors.affiliation: Advantar Laboratories, Inc, San Diego, CA 92121, USA. rkenley@advantarlabs.com
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kenley
authors.forename: Helena
authors.initials: H
authors.lastname: Filippone
authors.forename: Mai
authors.initials: M
authors.lastname: Giske
authors.forename: Dan
authors.initials: D
authors.lastname: Beidler
authors.forename: Joseph
authors.initials: J
authors.lastname: Vehige
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Fleitman
mesh_terms: D000577:Amides / Q000737:chemistry*; D000959:Antihypertensive Agents / Q000737:chemistry*; D000069580:Bimatoprost; D002851:Chromatography, High Pressure Liquid; D003008:Cloprostenol / Q000031:analogs & derivatives* / Q000737:chemistry; D003263:Contact Lenses, Hydrophilic; D020100:Hydrogels / Q000737:chemistry*; D009883:Ophthalmic Solutions / Q000737:chemistry*; D011460:Prostaglandins F / Q000737:chemistry*; D012828:Silicones / Q000737:chemistry*; D005466:Fluorocarbons
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D000069580:Bimatoprost; D003008:Cloprostenol; D020100:Hydrogels; D009883:Ophthalmic Solutions; D011460:Prostaglandins F; D012828:Silicones; C481129:lotrafilcon A; D005466:Fluorocarbons; C485333:tafluprost