Is phenylephrine pivalate a prodrug?

J. S. Mindel, S. T. Shaikewitz and S. M. Podos

Phenylephrine pivalate has been assumed to be a prodrug devoid of important intrinsic activity because of its structural similarity to dipivefrin (dipivaly 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 as consistent with the hypothesis that the phenylephrine pivalate molecule has important alpha-adrenergic activity regardless of whether it is converted to phenylephrine.