Ophthalmic epinephrine, phenylephrine, and pilocarpine affect the systemic absorption of ocularly applied timolol

Ocularly applied timolol eyedrops may cause serious systemic side-effects in some patients. In this study we evaluated the effects of pretreatment with epinephrine and pilocarpine eyedrops on systemic absorption of ophthalmic timolol. Epinephrine decreased the systemic absorption of timolol, while pilocarpine increased the peak concentrations of timolol in plasma. When applied in the same solution with timolol, pilocarpine had no effect and phenylephrine decreased the systemic absorption of timolol. The observed effects were due to the conjunctival and nasal vasoconstricting effects of epinephrine and phenylephrine and to the vasodilating effects of pilocarpine. These pharmacokinetic interactions demonstrate the importance of the conjunctival and nasal blood flow in the systemic absorption of timolol.