CLINICAL PHARMACOLOGY
Dipivefrin hydrochloride 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.
Dipivefrin is converted to epinephrine inside the human eye by enzyme hydrolysis. The liberated epinephrine, an adrenergic agonist, appears to exert its action by decreasing aqueous production and by enhancing outflow facility. The dipivefrin hydrochloride prodrug delivery system is a more efficient way of delivering the therapeutic effects of epinephrine, with fewer side effects than are associated with conventional epinephrine therapy.
The onset of action with one drop of dipivefrin hydrochloride ophthalmic solution occurs about 30 minutes after treatment, with maximum effect seen at about one hour.
Using a prodrug means that less drug is needed for therapeutic effect since absorption is enhanced with the prodrug. Dipivefrin hydrochloride, 0.1% was judged less irritating than a 1% solution of 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.
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