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Biomedical subjects

Joseph F Standing

Publications and source records attributed to Joseph F Standing.

5 recordsLinked to original sources
PubMed2026

Polymerase-inhibitor drug synergy and mutational signatures in different epithelial cell models of RSVA and hPIV3 infection.

Despite the huge global health burden presented by respiratory viruses, effective broad-spectrum antiviral therapeutic options remain limited. Here we evaluated the antiviral activity of four RNA-dependent RNA polymerase (RdRp) inhibitors, remdesivir, ribavirin, favipiravir, and molnupiravir, as monotherapy or dual-drug combinations against respiratory syncytial virus (subtype A, RSVA) and human parainfluenza (serotype 3, hPIV3) using epithelial cell lines and primary human airway culture models. Remdesivir showed the greatest potency across both viruses, while ribavirin and favipiravir also demonstrated inhibition. Molnupiravir was active against RSVA but not hPIV3. Several dual-drug combinations, including remdesivir-favipiravir, remdesivir-molnupiravir and favipiravir-molnupiravir, produced marked synergy against RSVA, and more limited synergy for hPIV3. Antiviral efficacy was validated in primary airway epithelial cultures, where effective concentrations preserved epithelial integrity and attenuated viral disruption of ciliary function. Across both viruses, increasing antiviral exposure was associated with dose-dependent signature mutagenesis. Antivirals induced significantly higher RSVA mutation burden in the primary airway model. These findings highlight the therapeutic potential of RdRp inhibitor combinations for RSVA and hPIV3, provide mechanistic insight through antiviral-related mutational signatures, and demonstrate advantages of the primary human airway culture model for development of effective multi-drug regimens and broad-spectrum antiviral preparedness.

Journal Article↗
PubMed2005

Paediatric formulations--getting to the heart of the problem.

Many medicines prescribed for children are unlicensed. Solid dosage forms present problems as children have difficulty swallowing whole tablets or capsules. When medicines are not licensed for children, it is unlikely that there will be a suitable, licensed liquid formulation and so extemporaneous liquid preparations (prepared at the dispensary or by GMP 'special' manufacturers) are often used. This study looked at a list of medicines commonly prescribed for children with cardiovascular conditions in an English specialist paediatric hospital and classified them according to licensed status and available formulations. As expected, most medicines used for children with cardiovascular problems were unlicensed and where this was the case, usually only 'special' liquids or extemporaneous preparations were available. Problems linked with formulations highlighted in this therapeutic category were: problems in dosing accuracy and unknown bioavailability of extemporaneous products, the use of potentially toxic excipients, and lack of access to modified release preparations for children. These problems are likely to extend to other paediatric therapeutic areas. There is currently a large, unmet need to improve formulations of commonly used paediatric medicines, both through licensing and standardising the production of extemporaneous and 'special' formulations. It is expected that the awaited European regulation will help to meet some of those needs.

Cardiovascular Agents↗
PubMed2005

Poor formulation information in published pediatric drug trials.

OBJECTIVE: The International Conference on Harmonisation Steering Committee recommends that appropriate formulations be used in pediatric drug trials. However, a lack of formulation research and/or economic constraints means that appropriate formulations are not always used. It is important for investigators who report the results of pediatric drug trials to provide sufficient information on the formulation and method of administration to ensure that the results can be reproduced in other clinical studies (reliability) and, more important, implemented in clinical practice (validity). The objective of this study was to evaluate whether pediatric formulation information was adequately reported in recent published trials of oral medicines that included children who were younger than 12 years. METHODS: Studies that were published between July 2002 and June 2004 in 10 highly cited journals (5 pediatric and 5 general medicine) were hand-searched and data were extracted independently by 2 reviewers according to a protocol. Papers that reported oral medication studies that included children who were younger than 12 years were classified as containing adequate, some, or no information on drug formulation. RESULTS: Of 3992 papers reviewed, 76 fulfilled the inclusion criteria. Only 28 (37%) gave adequate information for the study to be reproduced accurately, and 20 (26%) did not state the formulation used. When the formulation was reported, only 37 (49%) studies used a pediatric formulation (liquid, chewable tablet, granules). No significant differences between pediatric and general medical journals were seen, and no single journal consistently met the criteria for adequate information. CONCLUSION: Highly cited journals seem to permit inadequate formulation information in pediatric drug trials that they publish, impairing their validity and reliability. Authors should provide full formulation information in all pediatric clinical trial reports.

Child↗