![]() ![]() ![]() Consequently, long-acting formulations have become available, addressing the drawbacks of SA nifedipine preparations. ![]() The advantages of SA nifedipine use are the rapid onset of action and lack of central nervous system (CNS) depression however, the precipitous reduction in blood pressure means nifedipine is associated with adverse effects, including reflex tachycardia, retinal ischemia and myocardial ischemia and infarction. As opposed to concerns regarding the safety of SA nifedipine in adults, studies evaluating the safety of SA nifedipine in children suggest otherwise, with several studies concluding SA nifedipine to be an important, safe and effective oral antihypertensive agent. Other reports have also mentioned safety concerns with SA nifedipine preparations, associating its use with cerebral ischemia and myocardial infarction. The report concluded that the use of short-acting (SA) nifedipine in moderate to high doses resulted in an increase in total mortality in patients with coronary heart disease. In 1995, concerns regarding the safety of nifedipine surfaced after a meta-analysis of clinical trials of nifedipine was published. However, owing to safety and tolerability concerns and with the introduction of newer agents, the use of nifedipine has become less desirable. ![]() The use of nifedipine was once well established, being one of the most widely prescribed medicines to treat hypertension. 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. 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. 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. In order to pragmatically assess the translation of resultant dissolution profiles to the paediatric populations, virtual clinical trials simulations were conducted. 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. 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, 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. As a result, short acting nifedipine preparations are not recommended. 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. ![]()
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