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

Br J Dermatol. 2014 Jul;171(1):162-9. doi: 10.1111/bjd.12881. Epub 2014 Jul 16.

Abstract

Background: Persistent facial erythema is the most common primary pathological feature of rosacea, the only treatment for which is brimonidine tartrate (BT) gel.

Objectives: 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Adrenergic alpha-2 Receptor Agonists / administration & dosage
  • Adrenergic alpha-2 Receptor Agonists / blood
  • Adrenergic alpha-2 Receptor Agonists / pharmacokinetics*
  • Adult
  • Area Under Curve
  • Biological Availability
  • Brimonidine Tartrate
  • Drug Administration Schedule
  • Facial Dermatoses / drug therapy*
  • Facial Dermatoses / metabolism
  • Female
  • Gels
  • Humans
  • Male
  • Ophthalmic Solutions / pharmacokinetics*
  • Quinoxalines / administration & dosage
  • Quinoxalines / blood
  • Quinoxalines / pharmacokinetics*
  • Rosacea / drug therapy*
  • Rosacea / metabolism

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Gels
  • Ophthalmic Solutions
  • Quinoxalines
  • Brimonidine Tartrate