Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, NSW, 2007, Australia.
Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, NSW, 2007, Australia.
Chem Biol Interact. 2023 Feb 1;371:110351. doi: 10.1016/j.cbi.2023.110351. Epub 2023 Jan 12.
The pharmacokinetics of propranolol were investigated in obese and healthy weight groups. Research studies in relation to the presented topic were gathered, evaluated, and compared to distinguish variabilities involved amongst different lipophilic drugs and how they impacted the clinical effectiveness. Propranolol is a lipophilic drug so it was predicted that the pharmacokinetics would differ between obese and ideal-weight individuals. Previous research in other lipophilic drugs shows a trend to increase the volume of distribution and half-life in obese compared to ideal weight individuals. However, the majority of both clinical and preclinical studies gathered in this review, found a decrease in the volume of distribution (V) and clearance, and minimal significant difference in the half-life, in the obese group when compared with the ideal weight group. Different explanations for this comparison have been theorised including differing tissue blood flow, plasma protein binding, or hepatic clearance in obese compared with ideal weight populations; though the exact reasoning as to why propranolol does not follow the general trend for lipophilic drugs is yet to be determined. These findings regarding propranolol pharmacokinetics can be utilised towards further research and development in personalised medicine for patients with obesity and comorbid cardiovascular disease. The comparative studies highlighted the pharmacokinetic parameters which demonstrated a need for personalised dosage regimes for propranolol and a proposed research direction to understand why the difference exists between these population groups. With the prevalence of obesity continuing to rise, the relative pharmacokinetics of drugs must be evaluated in obese patient groups in order to inform drug dosing regimens and improve current clinical practice.
我们研究了肥胖和正常体重组人群中普萘洛尔的药代动力学。收集并评估了与所提出的课题相关的研究，以区分不同亲脂性药物之间的变异性及其对临床疗效的影响。普萘洛尔是一种亲脂性药物，因此预计其在肥胖和理想体重个体之间的药代动力学会有所不同。其他亲脂性药物的先前研究表明，与理想体重个体相比，肥胖个体的分布容积和半衰期呈增加趋势。然而，在这项综述中收集的大多数临床前和临床研究发现，与理想体重组相比，肥胖组的分布容积（V）和清除率降低，半衰期仅有微小的显著差异。对于这种比较，已经提出了不同的解释，包括肥胖与理想体重人群的组织血流、血浆蛋白结合或肝清除率不同；尽管尚未确定为什么普萘洛尔不符合亲脂性药物的一般趋势的具体原因。这些关于普萘洛尔药代动力学的发现可用于肥胖和合并心血管疾病患者的个体化医学的进一步研究和开发。比较研究突出了药代动力学参数，这些参数表明需要为普萘洛尔制定个体化剂量方案，并提出了一个研究方向，以了解为什么这些人群之间存在差异。随着肥胖的患病率持续上升，必须在肥胖患者群体中评估药物的相对药代动力学，以告知药物剂量方案并改进当前的临床实践。
