title: Pharmacodynamic equivalence study of two preparations of eye drops containing dorzolamide and timolol in healthy volunteers.
abstract: OBJECTIVE
  The aim of the present study was to assess the pharmacodynamic equivalence (lowering of intraocular pressure) of two preparations of eye drops containing 20 mg dorzolamide (CAS 120279-96-1) and 5 mg timolol (CAS 26839-75-8).
  
  
  METHODS
  The study was conducted as a monocentric, observer-blinded, randomized, single-dose, two-period crossover study in 38 healthy volunteers. Each volunteer received on day 1 in each period in a random way a single dose of 1 drop of the test or the reference formulation in the conjunctival sac of the right eye separated by a wash-out period of 7 days. Measurement of intraocular pressure (IOP) of the right eye (by a blinded observer) was performed on day 1 of each study period pre-dose and 2 h post dosing by means of Goldmann applanation tonometry. In order to investigate the pharmacodynamic equivalence of both products, the two-sided 95% confidence interval was calculated for the difference of the primary target parameter (absolute decrease in IOP 2 h post dose), by means of a parametric (ANOVA) statistical method.
  
  
  RESULTS
  The results of the statistical evaluation of the primary target parameter "absolute decrease in IOP 2 h post dose" demonstrated a decrease in the IOP of 4.72 mmHg for the eye treated with the test formulation (dorzolamide 20 mg/ml + timolol 5 mg/ml eye drops) and 4.61 mmHg for the treated with the reference formulation. The mean difference was 0.11 mmHg. The 95% confidence interval was between -0.33 and 0.55 mmHg and thus entirely within the pre-defined equivalence range (+/- 1.5 mmHg). The results of the statistical evaluation of the secondary target parameter relative (as % of baseline) decrease in IOP 2 h post dose demonstrated essentially similar effectiveness in lowering the IOP by 27.63% (test formulation) and 27.12% (reference formulation), respectively. Both drug products were well tolerated.
  
  
  CONCLUSIONS
  Both formulations showed comparable results obtained at a time probably equal to the maximum effect concerning the primary target parameter lowering of IOP 2 h post dose. The safety profile of both preparations showed no difference.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Medical University of Sofia, University Hospital Tsaritsa Joanna-ISUL, Bulgaria.
authors.forename: Emil
authors.initials: E
authors.lastname: Gatchev
authors.forename: Andrey
authors.initials: A
authors.lastname: Petrov
authors.forename: Emil
authors.initials: E
authors.lastname: Kolev
authors.forename: Russka
authors.initials: R
authors.lastname: Hristova
authors.forename: Irena
authors.initials: I
authors.lastname: Demircheva
authors.forename: Rossen
authors.initials: R
authors.lastname: Koytchev
authors.forename: Wolfram
authors.initials: W
authors.lastname: Richter
authors.forename: Friedrich
authors.initials: F
authors.lastname: Tegel
authors.forename: Ursula
authors.initials: U
authors.lastname: Thyroff-Friesinger
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005133:Eye Movements / Q000187:drug effects; D005260:Female; D005654:Fundus Oculi; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D011680:Pupil / Q000187:drug effects; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D013876:Thiophenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D013999:Timolol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014065:Tonometry, Ocular; D014792:Visual Acuity / Q000187:drug effects; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D002257:Carbonic Anhydrase Inhibitors; D009883:Ophthalmic Solutions; D013449:Sulfonamides; D013876:Thiophenes; D013999:Timolol; C062765:dorzolamide