Is Phenylephrine Pivalate a Prodrug?

Phenylephrine pivalate has been assumed to be a prodrug devoid of important intrinsic activity because of its structural similarity to dipivefrin (dipivalyl epinephrine). However, unlike dipivefrin, the pharmacologic activity of phenylephrine pivalate was not prevented by prior administration of echothiophate iodide. Rabbits pretreated bilaterally with 0.25% echothiophate for two and seven days had similar mydriasis, both in quantity and duration, after receiving 10% phenylephrine hydrochloride to one eye and 1% phenylephrine pivalate to the other eye. This was consistent with the hypothesis that the phenylephrine pivalate molecule has important α-adrenergic activity regardless of whether it is converted to phenylephrine.