Beta adrenergic antagonists and antianginal drugs

Stever, Lindsey M.; Demitraszek, Christopher J.; Murray, Sheena A.; Ali, A. N.

doi:10.1016/bs.seda.2021.08.015

Cited by 4 publications

(3 citation statements)

References 47 publications

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“…In order to pragmatically assess the impact of HPMC content on pharmacokinetics, dissolution profiles from formulations F1 (no HPMC), F2 (30% HPMC) and F3 (50% HPMC) mini-tablets were used to drive predictions of oral pharmacokinetics using the validated adult model. A dosage of 60 mg once daily and 30 mg twice daily was examined to identify an appropriate dosing approach to target the therapeutic range of 25–100 ng/mL [ 43 ] ( Figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

“…In order to assess the performance of the prepared formulations in adults, the dissolution profiles for F1 (no HPMC), F2 (30% HPMC) and F3 (50% HPMC) were incorporated into a virtual trial (−10 × 10 trial design n = 100) with healthy adults aged 20–50 years of age with dosing at either 30 mg twice daily or 60 mg once daily for 6 days. The impact of HPMC content on pharmacokinetics were subsequently assessed, in the context of maintenance of plasma concentrations within the purposed therapeutic range (25–100 ng/mL) [ 43 ].…”

Section: Methodsmentioning

confidence: 99%

“…Results were demarked for 5–7-year-olds and 7–11-year-olds. The impact of HPMC content on pharmacokinetics were subsequently assessed, in the context of maintenance of plasma concentrations within the purposed therapeutic range (25–100 ng/mL) [ 43 ].…”

Section: Methodsmentioning

confidence: 99%

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Virtual Clinical Trials Guided Design of an Age-Appropriate Formulation and Dosing Strategy of Nifedipine for Paediatric Use

et al. 2023

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The rapid onset of action of nifedipine causes a precipitous reduction in blood pressure leading to adverse effects associated with reflex sympathetic nervous system (SNS) activation, including tachycardia and worsening myocardial and cerebrovascular ischemia. As a result, short acting nifedipine preparations are not recommended. However, importantly, there are no modified release preparations of nifedipine authorised for paediatric use, and hence a paucity of clinical studies reporting pharmacokinetics data in paediatrics. Pharmacokinetic parameters may differ significantly between children and adults due to anatomical and physiological differences, often resulting in sub therapeutic and/or toxic plasma concentrations of medication. However, in the field of paediatric pharmacokinetics, the use of pharmacokinetic modelling, particularly physiological-based pharmacokinetics (PBPK), has revolutionised the ability to extrapolate drug pharmacokinetics across age groups, allowing for pragmatic determination of paediatric plasma concentrations to support drug licensing and clinical dosing. In order to pragmatically assess the translation of resultant dissolution profiles to the paediatric populations, virtual clinical trials simulations were conducted. In the context of formulation development, the use of PBPK modelling allowed the determination of optimised formulations that achieved plasma concentrations within the target therapeutic window throughout the dosing strategy. A 5 mg sustained release mini-tablet was successfully developed with the duration of release extending over 24 h and an informed optimised dosing strategy of 450 µg/kg twice daily. The resulting formulation provides flexible dosing opportunities, improves patient adherence by reducing frequent administration burden and enhances patient safety profiles by maintaining efficacious levels of consistent drug plasma levels over a sustained period of time.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%