Single-Dose Pharmacokinetics and Metabolism of the Oral Decongestant Phenylephrine HCl in Children and Adolescents
Abstract Introduction Pediatric data for phenylephrine, a decongestant used in cold medicines, are limited. This study characterized the pharmacokinetics and metabolism of phenylephrine HCl in children aged 2–17 years. Methods Forty-one children experiencing nasal congestion were dosed orally with p...
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| Format: | Article |
| Language: | English |
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Adis, Springer Healthcare
2022-12-01
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| Series: | Pulmonary Therapy |
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| Online Access: | https://doi.org/10.1007/s41030-022-00206-8 |
| _version_ | 1797863990388326400 |
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| author | Cathy K. Gelotte Dolly A. Parasrampuria Brenda A. Zimmerman |
| author_facet | Cathy K. Gelotte Dolly A. Parasrampuria Brenda A. Zimmerman |
| author_sort | Cathy K. Gelotte |
| collection | DOAJ |
| description | Abstract Introduction Pediatric data for phenylephrine, a decongestant used in cold medicines, are limited. This study characterized the pharmacokinetics and metabolism of phenylephrine HCl in children aged 2–17 years. Methods Forty-one children experiencing nasal congestion were dosed orally with phenylephrine HCl from 2.5 to 10 mg using a modified weight–age schedule. Plasma from blood samples collected up to 4.5 h after dosing was analyzed for phenylephrine. Urine collected over 24 h was analyzed for phenylephrine and metabolites. Blood pressure and pulse were measured after each blood sampling, and electrocardiograms were recorded before and after dosing. Pharmacokinetic parameters were estimated using noncompartmental methods. Results Mean phenylephrine total exposure (AUC∞) for children aged 2–5, 6–11, and 12–17 years was 672, 830, and 1020 pg∙h/mL, and mean maximum concentration (C max) was 477, 589, and 673 pg/mL, respectively. Times to peak concentration (T max) ranged from 0.17 to 1.5 h, and elimination half-life (t ½,β) was short from 1.2 to 1.6 h. Oral clearance (CL/F) increased with age, but with allometric scaling for body size, this trend reversed as scaled clearance (CL/F,scaled) was modestly higher in youngest children. No clinically relevant changes in vital signs or electrocardiograms were observed. Conclusion A dosing schedule with additional weight–age increments would provide more consistent systemic concentrations as children age and receive the next higher dose. No developmental delays in clearance mechanisms were apparent when oral clearance was scaled for body size. Phenylephrine pharmacokinetics and metabolism were consistent with adult data, although AUC∞ for the youngest group and C max for all pediatric groups were lower. Single doses of phenylephrine HCl were well tolerated. Trial Registration Clintrials.gov NCT00762567, registered 30 September 2008. |
| first_indexed | 2024-04-09T22:44:21Z |
| format | Article |
| id | doaj.art-fc96c5693a5d4ab6af015b4e23ed8597 |
| institution | Directory Open Access Journal |
| issn | 2364-1754 2364-1746 |
| language | English |
| last_indexed | 2024-04-09T22:44:21Z |
| publishDate | 2022-12-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Pulmonary Therapy |
| spelling | doaj.art-fc96c5693a5d4ab6af015b4e23ed85972023-03-22T11:59:42ZengAdis, Springer HealthcarePulmonary Therapy2364-17542364-17462022-12-019113915010.1007/s41030-022-00206-8Single-Dose Pharmacokinetics and Metabolism of the Oral Decongestant Phenylephrine HCl in Children and AdolescentsCathy K. Gelotte0Dolly A. Parasrampuria1Brenda A. Zimmerman2McNeil Consumer Healthcare, a Division of Johnson & Johnson Consumer, IncMcNeil Consumer Healthcare, a Division of Johnson & Johnson Consumer, IncMcNeil Consumer Healthcare, a Division of Johnson & Johnson Consumer, IncAbstract Introduction Pediatric data for phenylephrine, a decongestant used in cold medicines, are limited. This study characterized the pharmacokinetics and metabolism of phenylephrine HCl in children aged 2–17 years. Methods Forty-one children experiencing nasal congestion were dosed orally with phenylephrine HCl from 2.5 to 10 mg using a modified weight–age schedule. Plasma from blood samples collected up to 4.5 h after dosing was analyzed for phenylephrine. Urine collected over 24 h was analyzed for phenylephrine and metabolites. Blood pressure and pulse were measured after each blood sampling, and electrocardiograms were recorded before and after dosing. Pharmacokinetic parameters were estimated using noncompartmental methods. Results Mean phenylephrine total exposure (AUC∞) for children aged 2–5, 6–11, and 12–17 years was 672, 830, and 1020 pg∙h/mL, and mean maximum concentration (C max) was 477, 589, and 673 pg/mL, respectively. Times to peak concentration (T max) ranged from 0.17 to 1.5 h, and elimination half-life (t ½,β) was short from 1.2 to 1.6 h. Oral clearance (CL/F) increased with age, but with allometric scaling for body size, this trend reversed as scaled clearance (CL/F,scaled) was modestly higher in youngest children. No clinically relevant changes in vital signs or electrocardiograms were observed. Conclusion A dosing schedule with additional weight–age increments would provide more consistent systemic concentrations as children age and receive the next higher dose. No developmental delays in clearance mechanisms were apparent when oral clearance was scaled for body size. Phenylephrine pharmacokinetics and metabolism were consistent with adult data, although AUC∞ for the youngest group and C max for all pediatric groups were lower. Single doses of phenylephrine HCl were well tolerated. Trial Registration Clintrials.gov NCT00762567, registered 30 September 2008.https://doi.org/10.1007/s41030-022-00206-8PhenylephrinePharmacokineticsPediatricAdolescent |
| spellingShingle | Cathy K. Gelotte Dolly A. Parasrampuria Brenda A. Zimmerman Single-Dose Pharmacokinetics and Metabolism of the Oral Decongestant Phenylephrine HCl in Children and Adolescents Pulmonary Therapy Phenylephrine Pharmacokinetics Pediatric Adolescent |
| title | Single-Dose Pharmacokinetics and Metabolism of the Oral Decongestant Phenylephrine HCl in Children and Adolescents |
| title_full | Single-Dose Pharmacokinetics and Metabolism of the Oral Decongestant Phenylephrine HCl in Children and Adolescents |
| title_fullStr | Single-Dose Pharmacokinetics and Metabolism of the Oral Decongestant Phenylephrine HCl in Children and Adolescents |
| title_full_unstemmed | Single-Dose Pharmacokinetics and Metabolism of the Oral Decongestant Phenylephrine HCl in Children and Adolescents |
| title_short | Single-Dose Pharmacokinetics and Metabolism of the Oral Decongestant Phenylephrine HCl in Children and Adolescents |
| title_sort | single dose pharmacokinetics and metabolism of the oral decongestant phenylephrine hcl in children and adolescents |
| topic | Phenylephrine Pharmacokinetics Pediatric Adolescent |
| url | https://doi.org/10.1007/s41030-022-00206-8 |
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