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Dipivefrin is a member of a class of drugs known as prodrugs. Prodrugs are usually not active in themselves and require biotransformation to the parent compound before therapeutic activity is seen. These modifications are undertaken to enhance absorption, decrease side effects and enhance stability and comfort, thus making the parent compound a more useful drug. Enhanced absorption makes the prodrug a more efficient delivery system for the parent drug because less drug will be needed to produce the desired therapeutic response.
Dipivefrin is a prodrug of epinephrine formed by the diesterification of epinephrine and pivalic acid. The addition of pivaloyl groups to the epinephrine molecule enhances its lipophilic character and as a consequence, its penetration into the anterior chamber of the eye.
Dipivefrin is converted to epinephrine inside the human eye by enzyme hydrolysis. The liberated epinephrine, an adrenergic agonist, appears to exert its action on intraocular pressure by decreasing aqueous humor production and by enhancing outflow facility. The dipivefrin prodrug delivery system is a more efficient way of delivering the therapeutic effects of epinephrine, with fewer side effects than are usually associated with conventional epinephrine therapy.
The onset of action with one drop of dipivefrin occurs about 30 minutes after treatment, with maximum effect seen at about 1 hour.
Using dipivefrin means that less drug is needed for therapeutic effect since absorption is enhanced with the prodrug. 0.1% dipivefrin was judged less irritating than 1% epinephrine hydrochloride or bitartrate. In addition, only 8 of 455 patients (1.8%) treated with dipivefrin reported discomfort due to photophobia, glare or light sensitivity.
In controlled and open label studies of glaucoma, dipivefrin demonstrated a statistically significant intraocular pressure-lowering effect. Patients using dipivefrin twice daily in studies with mean durations of 76 to 146 days experienced mean pressure reductions ranging from 20 to 24%.
Therapeutic response to dipivefrin twice daily is somewhat less than 2% epinephrine twice daily. Controlled studies showed statistically significant differences in lowering of intraocular pressure between dipivefrin and 2% epinephrine. In controlled studies in patients with a history of epinephrine intolerance, only 3% of patients treated with dipivefrin exhibited intolerance, while 55% of those treated with epinephrine again developed intolerance.
Therapeutic response to dipivefrin twice daily therapy is comparable to 2% pilocarpine 4 times daily. In controlled clinical studies comparing dipivefrin and 2% pilocarpine there were no statistically significant differences in the maintenance levels of IOP for the two medications. Dipivefrin does not produce miosis or accommodative spasm which cholinergic agents are known to produce. The blurred vision and night blindness often associated with miotic agents are not present with dipivefrin therapy. Patients with cataracts avoid the inability to see around lenticular opacities caused by a constricted pupil.
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