Prophylaxis of Gout Flares in Patients with Renal Impairment: Dosing Adjustments with Colchicine Oral Solution Informed by a Pharmacokinetic Model.
IF 2.9
3区 医学
Q2 RHEUMATOLOGY
引用次数: 0
Abstract
Introduction: Patients receiving the standard prophylaxis dose of colchicine for gout flares are at increased risk for developing toxicity if there are pre-existing renal impairment or drug-drug interactions. Guidelines recommend exercising caution, deferring dose adjustment to the clinician's discretion.
Methods: Pharmacokinetic study data for colchicine oral solution in healthy subjects was used to build a pharmacokinetic model. Using the derived pharmacokinetic disposition parameters from the best fit model and the derived parameters of clearance in patients with renal impairment, simulation of colchicine plasma levels to target 0.5-3 ng/mL with colchicine oral solution was undertaken for various dose levels in different degrees of renal impairment.
Results: With the standard colchicine 0.6 mg daily dose, plasma levels are expected to be therapeutic in patients with mild renal impairment (estimated glomerular filtration rate [eGFR] 60-89 mL/min/1.73 m2). However, with this same 0.6 mg daily dose, patients with moderate renal impairment (eGFR 30-59 mL/min/1.73 m2) and severe renal impairment (eGFR of 15-29 mL/min/1.73 m2) would have excursions up to 10% and 36%, respectively, above the maximum tolerated level. Administering a lower dose such as 0.3 mg daily by splitting the conventional 0.6 mg tablet or by administering 0.6 mg once every-other-day (QOD) in moderate renal impairment would result in plasma colchicine levels in subtherapeutic range (< 0.5 ng/mL) for 20-70% of the dosing interval.
Conclusion: Analysis of pharmacokinetic model data confirms that the majority of patients with renal impairment taking colchicine solid dosage formulations will be above or below therapeutic levels, exposing them to potential side effects. However, more precise dosing with colchicine oral solution of 0.48 mg (4 mL) or 0.5 mg tablet available in certain countries for moderate renal impairment and 0.3 mg (2.5 mL) for severe renal impairment are associated with optimal levels and safer for patients with renal impairment. No dosage adjustment is needed for patients with mild renal impairment.
肾损害患者痛风发作的预防：秋水仙碱口服溶液剂量调整的药代动力学模型。
引言：接受秋水仙碱标准预防剂量治疗痛风发作的患者，如果存在预先存在的肾脏损害或药物-药物相互作用，则发生毒性的风险增加。指南建议谨慎使用，将剂量调整推迟到临床医生的判断。方法：采用秋水仙碱口服液在健康人体内的药动学研究数据，建立药动学模型。利用最佳拟合模型导出的药代动力学配置参数和肾损害患者清除率的导出参数，模拟不同剂量的秋水仙碱口服液在不同程度肾损害下，秋水仙碱血浆水平达到0.5 ~ 3 ng/mL目标。结果：在标准秋水仙碱每日0.6 mg剂量下，血浆水平预计对轻度肾功能损害患者有治疗作用（估计肾小球滤过率[eGFR] 60-89 mL/min/1.73 m2）。然而，在相同的0.6 mg日剂量下，中度肾功能损害（eGFR 30-59 mL/min/1.73 m2）和重度肾功能损害（eGFR 15-29 mL/min/1.73 m2）患者的剂量偏差将分别高于最大耐受水平10%和36%。给药剂量较低，如每日0.3 mg，将常规的0.6 mg片剂分开服用，或在中度肾功能损害时每隔一天给药0.6 mg，会导致血浆秋水仙碱水平处于亚治疗范围(结论：药代动力学模型数据分析证实，大多数肾损害患者服用秋水仙碱固体剂型将高于或低于治疗水平，暴露于潜在的副作用中。然而，更精确的秋水仙碱口服溶液剂量为0.48 mg （4ml）或0.5 mg片剂，在某些国家用于中度肾功能损害，0.3 mg （2.5 mL）用于重度肾功能损害，与最佳水平相关，对肾功能损害患者更安全。轻度肾功能损害患者无需调整剂量。
本文章由计算机程序翻译，如有差异，请以英文原文为准。
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来源期刊
Rheumatology and Therapy
RHEUMATOLOGY-
CiteScore
6.00
自引率
5.30%
发文量
91
审稿时长
6 weeks
期刊介绍：
Aims and Scope
Rheumatology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of rheumatologic therapies. Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed.
Areas of focus include, but are not limited to, rheumatoid arthritis, gout, gouty arthritis, psoriatic arthritis, osteoarthritis, juvenile idiopathic/rheumatoid arthritis, systemic lupus erythematosus, axial spondyloarthritis, Pompe’s disease, inflammatory joint conditions, musculoskeletal conditions, systemic sclerosis, and fibromyalgia.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial protocols, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Rheumatology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
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The journal is a member of the Committee on Publication Ethics (COPE) and subscribes to its principles on how to deal with acts of misconduct thereby committing to investigate allegations of misconduct in order to ensure the integrity of research. Content in this journal is peer-reviewed (Single-blind). For more information on our publishing ethics policies, please see here: https://www.springer.com/gp/editorial-policies
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