Phenylephrine hydrochloride (HCl) is a decongestant that is available as the over-the-counter (OTC) medicines. It was earlier marketed as the prescription product that contained phenylephrine tannate, an extended-release salt, allowing dosing every 8-12 hours. According to the regulatory history, the cold medicines which were marketed before 1962 had inadequate supporting clinical data. There has been an extensive replacement of pseudoephedrine by phenylephrine in OTC products in the last ten years as the requirement for contemporary studies also grew.

The objective of the experimental crossover study was to assess the effects of salt form, acetaminophen and food on phenylephrine pharmacokinetics and metabolites in healthy individuals. The test treatment group were given 25 mg phenylephrine tannate (equivalent to 10 mg phenylephrine HCl) in combination with 200 mg guaifenesin, fasted; 10 mg phenylephrine HCl in combination with 650 mg acetaminophen, fasted and 10 mg phenylephrine HCl given in fed. The reference treatment group was 10 mg phenylephrine HCl, fasted. Plasma phenylephrine pharmacokinetics along with urine metabolites were determined. Even though the tannate salt slowed the phenylephrine absorption as compared with the HCl salt, the terminal concentrations were almost similar, which suggested that products containing the tannate salt should not be dosed less often than those that contain the HCl salt. Thus, the evidence that acetaminophen increases phenylephrine bioavailability by opposing the pre-systemic sulfation was verified by increased phenylephrine sulfate in urine. The phenylephrine absorption was delayed by food, but not the total amount that was absorbed.

Source: Gelotte CK. An open-label, randomized, four-treatment crossover study evaluating the effects of salt form, acetaminophen, and food on the pharmacokinetics of phenylephrine. Regul Toxicol Pharmacol. 2018 Jun;95:333-338.