Single-Dose Pharmacokinetics and Metabolism of the Oral Decongestant Phenylephrine HCl in Children and Adolescents.

IF 2.3 Q2 RESPIRATORY SYSTEM

Pulmonary Therapy Pub Date : 2023-03-01 DOI:10.1007/s41030-022-00206-8

Cathy K Gelotte, Dolly A Parasrampuria, Brenda A Zimmerman

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引用次数: 2

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.

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儿童和青少年口服减充血剂盐酸苯肾上腺素的单剂量药代动力学和代谢。

导论:用于感冒药的减充血剂苯肾上腺素的儿科数据有限。本研究对盐酸苯肾上腺素在2-17岁儿童体内的药代动力学和代谢进行了研究。方法:41例鼻塞患儿采用改良体重-年龄表口服盐酸苯肾上腺素2.5 ~ 10 mg。在给药后4.5小时采集血液样本，分析血浆中是否含有苯肾上腺素。收集24小时尿液，分析苯肾上腺素及其代谢物。每次采血后测量血压、脉搏，记录给药前后心电图。采用非区室法估计药代动力学参数。结果:2-5岁、6-11岁和12-17岁儿童苯肾上腺素平均总暴露量(AUC∞)分别为672、830和1020 pg∙h/mL，平均最大浓度(Cmax)分别为477、589和673 pg/mL。达到峰值浓度的时间(Tmax)从0.17到1.5小时不等，消除半衰期(t½，β)从1.2到1.6小时不等。口服清除率(CL/F)随着年龄的增长而增加，但随着体型的异速缩放，这种趋势逆转，最小的儿童的清除率(CL/F，缩放)略高。生命体征和心电图均未见临床相关变化。结论:随着儿童年龄的增长和接受下一个更高的剂量，增加体重-年龄增量的给药方案将提供更一致的全身浓度。当口服清除率与身体大小成比例时，清除率机制没有明显的发育延迟。苯肾上腺素的药代动力学和代谢与成人数据一致，尽管最年轻组的AUC∞和所有儿科组的Cmax都较低。单剂量盐酸苯肾上腺素耐受性良好。试验注册:Clintrials.gov NCT00762567，注册于2008年9月30日。

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来源期刊

Pulmonary Therapy Medicine-Pulmonary and Respiratory Medicine

CiteScore

5.20

自引率

3.30%

发文量

审稿时长

6 weeks

期刊介绍： Aims and Scope Pulmonary Therapy is an international, open access, peer-reviewed (single-blind), and rapid publication journal. The scope of the journal is broad and will consider all scientifically sound research from pre-clinical, clinical (all phases), observational, real-world, and health outcomes research around the use of pulmonary therapies, devices, and surgical techniques. Areas of focus include, but are not limited to: asthma; chronic obstructive pulmonary disease; idiopathic pulmonary fibrosis; pulmonary hypertension; cystic fibrosis; lung cancer; respiratory tract disorders; allergic rhinitis and other respiratory allergies; influenza, pneumococcal infection, respiratory syncytial virus and other respiratory infections; and inhalers and other device therapies. The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/series, trial protocols and short communications such as commentaries and editorials. Pulmonary Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of quality research, which may be considered of insufficient interest by other journals. Rapid Publication The journal’s publication timelines aim for a rapid peer review of 2 weeks. If an article is accepted it will be published 3–4 weeks from acceptance. The rapid timelines are achieved through the combination of a dedicated in-house editorial team, who manage article workflow, and an extensive Editorial and Advisory Board who assist with peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid, efficient communication of the latest research and reviews, fostering the advancement of pulmonary therapies. Open Access All articles published by Pulmonary Therapy are open access. Personal Service The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning authors will always have an editorial contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE, GPP and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. Digital Features and Plain Language Summaries Pulmonary Therapy offers a range of additional features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by key summary points, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand the scientific content and overall implications of the article. The journal also provides the option to include various types of digital features including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations. All additional features are peer reviewed to the same high standard as the article itself. If you consider that your paper would benefit from the inclusion of a digital feature, please let us know. Our editorial team are able to create high-quality slide decks and infographics in-house, and video abstracts through our partner Research Square, and would be happy to assist in any way we can. For further information about digital features, please contact the journal editor (see ‘Contact the Journal’ for email address), and see the ‘Guidelines for digital features and plain language summaries’ document under ‘Submission guidelines’. For examples of digital features please visit our showcase page https://springerhealthcare.com/expertise/publishing-digital-features/ Publication Fees Upon acceptance of an article, authors will be required to pay the mandatory Rapid Service Fee of €4500/ $5100/ £3650. The journal will consider fee discounts and waivers for developing countries and this is decided on a case by case basis. Peer Review Process Upon submission, manuscripts are assessed by the editorial team to ensure they fit within the aims and scope of the journal and are also checked for plagiarism. All suitable submissions are then subject to a comprehensive single-blind peer review. Reviewers are selected based on their relevant expertise and publication history in the subject area. The journal has an extensive pool of editorial and advisory board members who have been selected to assist with peer review based on the afore-mentioned criteria. At least two extensive reviews are required to make the editorial decision, with the exception of some article types such as Commentaries, Editorials, and Letters which are generally reviewed by one member of the Editorial Board. Where reviewer recommendations are conflicted, the editorial board will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed). Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case-by-case basis and should be sent to the journal editor. Preprints We encourage posting of preprints of primary research manuscripts on preprint servers, authors’ or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. Posting of preprints is not considered prior publication and will not jeopardize consideration in our journals. Authors should disclose details of preprint posting during the submission process or at any other point during consideration in one of our journals. Once the manuscript is published, it is the author’s responsibility to ensure that the preprint record is updated with a publication reference, including the DOI and a URL link to the published version of the article on the journal website. Please follow the link for further information on preprint sharing: https://www.springer.com/gp/authors-editors/journal-author/journal-author-helpdesk/submission/1302#c16721550 Copyright Pulmonary Therapy''s content is published open access under the Creative Commons Attribution-Noncommercial License, which allows users to read, copy, distribute, and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited. The author assigns the exclusive right to any commercial use of the article to Springer. For more information about the Creative Commons Attribution-Noncommercial License, click here: http://creativecommons.org/licenses/by-nc/4.0. Contact For more information about the journal, including pre-submission enquiries, please contact christopher.vautrinot@springer.com.