title: Comparative pharmacokinetics and bioavailability of brimonidine following ocular and dermal administration of brimonidine tartrate ophthalmic solution and gel in patients with moderate-to-severe facial erythema associated with rosacea.
abstract: BACKGROUND
  Persistent facial erythema is the most common primary pathological feature of rosacea, the only treatment for which is brimonidine tartrate (BT) gel.
  
  
  OBJECTIVE
  To assess the relative bioavailability of topical BT gel in comparison with the ophthalmic BT solution.
  
  
  METHODS
  A pharmacokinetic study was conducted to compare intraindividual systemic exposures after dermal application of BT gel (0·07%, 0·18% and 0·5%) under maximal use conditions in patients with moderate-to-severe facial erythema associated with rosacea, and administration of BT ophthalmic solution 0·2%.
  
  
  RESULTS
  Patients who received BT ophthalmic solution 0·2% three times a day for 1 day had a mean Cmax of 54 ± 28 pg mL(-1) and a mean 0-24-h area under the curve (AUC0-24 h ) of 568 ± 277 pg h mL(-1) . Topical application of BT gel for 29 days resulted in quantifiable systemic exposure in 22%, 48%, 71% and 79% of patients who received BT gel 0·07% twice daily, 0·18% once daily, 0·18% twice daily and 0·5% once daily, respectively. The mean Cmax values for the BT gels ranged between 13 and 25 pg mL(-1) , and mean AUC0-24 h values ranged between 42 and 290 pg h mL(-1) . Systemic exposure increased with applied dose, with no drug accumulation for the duration of treatment. The systemic exposure observed with the highest dose of BT gel (0·5% once daily) was significantly lower than the systemic levels observed for the ophthalmic solution. 0·2% apply for all the concentrations.
  
  
  CONCLUSIONS
  The systemic safety profile of BT gel may be considered better than that of the ophthalmic solution.
authors: Galderma R&D, Sophia Antipolis, France.
authors: K
authors: K
authors: Benkali
authors: M
authors: M
authors: Leoni
authors: F
authors: F
authors: Rony
authors: R
authors: R
authors: Bouer
authors: A
authors: A
authors: Fernando
authors: M
authors: M
authors: Graeber
authors: N
authors: N
authors: Wagner
mesh_terms: D000279:Administration, Cutaneous; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D000068438:Brimonidine Tartrate; D004334:Drug Administration Schedule; D005148:Facial Dermatoses / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005782:Gels; D006801:Humans; D008297:Male; D009883:Ophthalmic Solutions / Q000493:pharmacokinetics*; D011810:Quinoxalines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012393:Rosacea / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D005782:Gels; D009883:Ophthalmic Solutions; D011810:Quinoxalines; D000068438:Brimonidine Tartrate