The categorical assessments of pulse and blood pressure outside reference limits were comparable among the single oral doses of phenylephrine HCl 10, 20, and 30 mg, placebo, and baseline. Means of time-matched differences in pulse and blood pressure from baseline showed similar fluctuations over 12 h among phenylephrine HCl doses and placebo. Initially, small increases in mean blood pressure up to 40 min coincided with small decreases in mean pulse up to 20 min.
Maximum increases in mean pulse and blood pressure were observed between 6 and 7 h, respectively, for all treatments, reflecting the acrophase or high point of diurnal variation that typically occurs daily at around h [ 13 ]. The main purpose of serial measurements of pulse, blood pressure, and ECGs was to assess cardiovascular tolerability of single doses of phenylephrine at the main therapeutic and two higher doses.
As such, this study was not designed to thoroughly evaluate the QTc interval, which would require multiple dosing, inclusion of a positive control, replicate ECGs at each timepoint to lower variability, and ECG over-read by qualified cardiologists [ 14 , 16 ].
Therefore, these results do not appropriately address potential proarrhythmic risk due to phenylephrine. In the current study, single ECGs were recorded at ten timepoints per subject during baseline and again on each subsequent treatment day. Therefore, in addition to the incidences of QTcF values within and above the reference limits being similar among treatments, the percentages of subjects with at least one observation within and above the categorical limits are consistent with the study design and QTcF variability.
The remaining values were borderline ms and high ms in two female subjects and high ms in a male subject. Both high values were recorded 10 h after the dose when phenylephrine plasma concentrations were either negligible or non-existent, and within an hour of the evening meal [ 14 , 18 ]. Overall, the cardiovascular assessments showed no, or minimal, effects following single doses of phenylephrine HCl 10, 20, and 30 mg. A review of heart rate and blood pressure from a series of placebo-controlled, nasal decongestant studies showed statistically significant differences from baseline following doses of phenylephrine HCl 10 and 25 mg [ 22 ].
However, these changes were relatively small and inconsistent with regard to increases or decreases over the measurement interval, and did not account for diurnal variation with time-matched baselines. In a study on a pharmacokinetic drug interaction between phenylephrine and acetaminophen, researchers were unable to show any change in mean arterial blood pressure in the healthy volunteers for phenylephrine concentrations in the range expected for a 20 mg dose [ 7 ].
Finally, the cardiovascular assessments in this and other studies of therapeutic doses are in accordance with published reports that found higher single oral doses from 40 to mg are necessary for consistent, clinically meaningful cardiovascular effects [ 3 , 4 ].
The single-dose pharmacokinetics of phenylephrine HCl 10, 20, and 30 mg in this study confirmed the rapid absorption and elimination of phenylephrine reported previously for the 10 mg dose.
Maximum and total systemic exposures following the three doses of phenylephrine HCl increased disproportionally with increasing dose. The increases in plasma concentrations, along with decreases in urinary excretion of the sulfate conjugate, suggest that more phenylephrine may bypass intestinal-wall metabolism at the higher doses.
Single oral doses of phenylephrine HCl 10, 20, and 30 mg were well-tolerated in this study. No serious adverse events were reported, and only one event, mild somnolence, was rated as possibly related to phenylephrine HCl.
No incidences of pulse, blood pressure, or QTcF outside of reference limits were deemed clinically significant. The study was conducted in accordance with guidelines of the International Conference on Harmonisation—Good Clinical Practice and local Canadian laws on clinical research involving human subjects. All subjects were informed of the nature and purpose of the study, and gave written informed consent to participate before any screening procedures.
National Center for Biotechnology Information , U. Clinical Drug Investigation. Clin Drug Investig. Published online Aug Cathy K. Gelotte and Brenda A. Brenda A. Author information Copyright and License information Disclaimer. Gelotte, Email: moc. Corresponding author. This article has been cited by other articles in PMC.
Abstract Background and Objectives Phenylephrine HCl 10 mg has been used as a nasal decongestant for over 50 years, yet only limited pharmacokinetic and metabolic data are available.
Methods Twenty-eight adults were enrolled in this randomized, double-blind, placebo-controlled, single-dose, four-treatment crossover study. Results After oral administration, phenylephrine was rapidly absorbed with median times to maximum plasma concentrations t max from 0. Conclusions Maximum and total systemic exposures following singe doses of phenylephrine HCl 10, 20, and 30 mg increased disproportionally with increasing dose.
Key Points Phenylephrine HCl 10 mg, a nasal decongestant, was developed in the s and not subject to current clinical and regulatory standards for market approval. Therefore, pharmacokinetic and metabolic data on therapeutic and higher doses are limited or non-existent. Maximum and total systemic exposures following the three doses of phenylephrine HCl 10, 20, and 30 mg increased disproportionally with increasing dose. Cardiovascular tolerability, as measured by serial pulse, blood pressure, and electrocardiograms over 12 h, was comparable among single oral doses of phenylephrine HCl 10, 20, and 30 mg and placebo.
Open in a separate window. Introduction Phenylephrine HCl is indicated for the temporary relief of nasal congestion caused by the common cold or allergic rhinitis. Sample Collection and Assays For the pharmacokinetic analysis, blood samples were collected at 0 predose , 10, 15, 20, 25, 30, and 40 min and 1, 1. Cardiovascular Assessments Cardiovascular assessments included measurements of pulse, blood pressure, and ECGs over 12 h after each treatment dose.
Safety Assessments Subjects were screened for health status by physical examination, vital signs, ECGs, and clinical laboratory tests hematology, chemistry, and urinalysis. Results Subjects Twenty-eight subjects 13 male and 15 female enrolled in the study, of whom 27 subjects completed four treatments.
Pharmacokinetics Mean plasma concentration—time profiles following single-dose administration of phenylephrine HCl 10, 20, and 30 mg are shown in Fig.
Table 1 Pharmacokinetic parameters after a single oral administration of phenylephrine HCl. Pulse and Blood Pressure Assessments The incidence count and percentage of subjects with pulse or blood pressure values below and above the reference limits were comparable at baseline, and after placebo and the three phenylephrine HCl doses Table 2.
Table 2 Incidence count and percentage of subjects with pulse or blood pressure outside reference limits. Safety Over the range of single phenylephrine HCl doses evaluated in this study, no cardiovascular assessments outside of reference limits were deemed clinically significant by the investigator.
Discussion Following single-dose oral administration, phenylephrine was rapidly absorbed from the 10, 20, and 30 mg doses, with C max occurring between 13 and 60 min. Conclusion The single-dose pharmacokinetics of phenylephrine HCl 10, 20, and 30 mg in this study confirmed the rapid absorption and elimination of phenylephrine reported previously for the 10 mg dose.
Ethical approval The study was conducted in accordance with guidelines of the International Conference on Harmonisation—Good Clinical Practice and local Canadian laws on clinical research involving human subjects. Informed consent All subjects were informed of the nature and purpose of the study, and gave written informed consent to participate before any screening procedures. References 1. The pharmacology of a-adrenergic decongestants.
Nasal decongestants. Non-prescription sympathomimetic agents and hypertension. Med Toxicol. Keys A, Violante A. The cardio-circulatory effects in man of neo-synephrin. J Clin Invest. Hengstmann JH, Goronzy J. Pharmacokinetics of 3H-phenylephrine in man. Eur J Clin Pharmacol. Ptacek P, Macek JK.
Development and validation of a liquid chromatography-tandem mass spectrometry method for the determination of phenylephrine in human plasma and its application to a pharmacokinetic study. J Chromatogr B. Increased bioavailability of phenylephrine by co-administration of acetaminophen: results of four open-label, crossover pharmacokinetic trials in healthy volunteers. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location — one that is up and away and out of their sight and reach.
Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. In case of overdose, call the poison control helpline at If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at It is important for you to keep a written list of all of the prescription and nonprescription over-the-counter medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements.
You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies. Federal law generally requires that prescription drugs in the U. Generic alternatives may be available. Phenylephrine pronounced as fen il ef' rin. Why is this medication prescribed? How should this medicine be used? Other uses for this medicine What special precautions should I follow?
What special dietary instructions should I follow? What should I do if I forget a dose? What side effects can this medication cause? What should I know about storage and disposal of this medication? Brand names Brand names of combination products. Other uses for this medicine. What special precautions should I follow? Before taking phenylephrine, tell your doctor and pharmacist if you are allergic to phenylephrine, any other medications, or any of the ingredients in phenylephrine preparations.
When using this product, do not exceed recommended dose. Stop use and ask a doctor if nervousness, dizziness, or sleeplessness occur symptoms do not improve within 7 days or occur with a fever. If pregnant or breast-feeding, ask a health professional before use.
Keep out of reach of children. Do not take more than 6 tablets in 24 hours. Version Files Mar 19, 4 current download Jun 11, 2 download Aug 30, 1 download. NDC 1 inactivated 2 inactivated 3 inactivated. Product Information.
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