Can a fraction of the dolutegravir dispersible tablet solution be used to dose neonates?

Author:

Phogole Cassius M.1,Bekker Adrie2,Cressey Tim R.3,Ferris William1,Decloedt Eric1,Kellermann Tracy1ORCID

Affiliation:

1. Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa;

2. Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa;

3. AMS-PHPT Research Collaboration, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand

Abstract

Background: The smallest dolutegravir (DTG) dose approved is 5 mg once-daily in infants ≥4 weeks and weighing ≥3 to <6kg using a dispersible tablet (DT). Neonates (<28 days of life) may require a lower dose due to immature organ development. We evaluated the aqueous dispersibility of the generic DTG-DT 10 mg scored tablets (Viatris Inc.) to determine the possibility of uniform concentrations that could allow for lower daily doses in neonates. Methods: Each 5 mL polypropylene tube had DTG-DT 5 mg dissolved in 5 mL ultrapure water. Tubes were labelled with three ‘zones’ (bottom: 0-1 mL; middle: 1-3 mL; top: 3-5 mL). Suspensions were mixed by swirling, or swirling with either a syringe-pump, vortexing, or sonication. DTG concentration in each zone was determined using high-performance liquid chromatography. Tubes were rinsed with 1 mL acetonitrile to determine the residual drug. Acceptable criteria for percentage difference was set at ≤20% according to European Medicines Agency guidelines. Results: Dispersion of DTG-DT in water did not remain homogeneous, resulting in DTG concentrations that varied by over 50% across the three zones within the tubes. Rapid sedimentation was observed shortly after mixing. Furthermore, it was found that 24% to 35% of the DTG residue remained adhered to the tube after the aqueous dispersion had been eluted, highlighting the importance of the rinse step. Conclusion: Aqueous dispersion of the DTG-DT is not uniform and displays a high degree of sedimentation. It is therefore not possible to administer a fraction of the dispersion (lower DTG dose) to neonates by using this formulation.

Publisher

Ovid Technologies (Wolters Kluwer Health)

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3