药代动力学
左旋多巴
最大值
交叉研究
卡比多巴
药效学
医学
吸收(声学)
口服
药理学
生物利用度
帕金森病
化学
内科学
材料科学
安慰剂
疾病
替代医学
复合材料
病理
作者
Peter A. LeWitt,Aaron Ellenbogen,Daniel Burdick,Steven A. Gunzler,Ramon Gil,Rohit Dhall,Ghazal Banisadr,Richard D’Souza
标识
DOI:10.1016/j.prdoa.2023.100197
摘要
IPX203 is a novel oral extended-release (ER) formulation of carbidopa (CD) and levodopa (LD) developed to address the short half-life and limited area for absorption of LD in the gastrointestinal tract. This paper presents the formulation strategy of IPX203 and its relationship to the pharmacokinetics (PK) and pharmacodynamic profile of IPX203 in Parkinson's disease (PD) patients.IPX203 was developed with an innovative technology containing immediate-release (IR) granules and ER beads that provides rapid LD absorption to achieve desired plasma concentration and maintaining it within the therapeutic range for longer than can be achieved with current oral LD formulations. The PK and pharmacodynamics of IPX203 were compared with IR CD-LD in a Phase 2, open-label, rater-blinded, multicenter, crossover study in patients with advanced PD.Pharmacokinetic data showed that on Day 15, LD concentrations were sustained above 50% of peak for 6.2 h with IPX203 vs. 3.9 h with IR CD-LD (P = 0.0002). Pharmacodynamic analysis demonstrated that mean MDS-UPDRS Part III scores prior to administration of the first daily dose were significantly lower among patients receiving IPX203 than IR CD-LD (LS mean difference -8.1 [25.0], P = 0.0255). In a study conducted in healthy volunteers, a high-fat, high-calorie meal delayed plasma LD Tmax by 2 h, and increased Cmax and AUCtau by approximately 20% compared with a fasted state. Sprinkling capsule contents on applesauce did not affect PK parameters.These data confirm that the unique design of IPX203 addresses some of the limitations of oral LD delivery.
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