Wagner Claudia C, Rusca Antonio, Kletter Kurt, Tschurlovits Manfred, Pace Silvia, Longo Antonio, Pedrani Massimo, Villa Roberto, Frimonti Enrico, Müller Markus, Brunner Martin
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Xenobiotica. 2011 Nov;41(11):988-95. doi: 10.3109/00498254.2011.597454. Epub 2011 Aug 3.
Propionyl-L-carnitine is a naturally occurring analogue of L-carnitine (LC) produced in the body. PLC administration has shown beneficial effects in cardiovascular pathologies. In ulcerative colitis (UC), oral PLC treatment increased clinical presentation and positively influenced colon histology. In the present study, the MMX Multi Matrix System® (MMX™) was used as drug delivery strategy for targeted PLC colon delivery. A pharmacoscintigraphic study (n = 6 healthy volunteers) described release characteristics of two MMX-PLC-HCl controlled release 500 mg tablets. A pharmacokinetic (PK) parallel group study (n = 24) determined safety, plasma PLC concentrations and PK parameters after single and multiple doses. Gastrointestinal transit was slow and variable. The colon was the main site of PLC release and absorption. After single 500 or 1000 mg PLC doses plasma PLC and LC increased up to 2.6 and 1.2-1.3-fold compared to baseline. Multiple doses of 500 and 1000 mg twice a day over 7 days did not significantly increase maximum plasma concentrations of PLC or LC with respect to concentrations achieved after single dose administration. The colon is the main site of PLC release and absorption from MMX-PLC tablets. A daily dose of 500 mg to 1000 mg PLC twice a day was well tolerated, justifying further studies in patients with pathologies of the distal gastrointestinal tract to evaluate the efficacy of the MMX-PLC formulation.
丙酰-L-肉碱是体内产生的L-肉碱（LC）的天然类似物。丙酰-L-肉碱给药已显示出对心血管疾病的有益作用。在溃疡性结肠炎（UC）中，口服丙酰-L-肉碱治疗改善了临床表现，并对结肠组织学产生了积极影响。在本研究中，MMX多矩阵系统®（MMX™）被用作靶向丙酰-L-肉碱结肠递送的药物递送策略。一项药物闪烁扫描研究（n = 6名健康志愿者）描述了两种MMX-丙酰-L-肉碱盐酸盐控释500 mg片剂的释放特性。一项药代动力学（PK）平行组研究（n = 24）确定了单剂量和多剂量给药后的安全性、血浆丙酰-L-肉碱浓度和PK参数。胃肠道转运缓慢且多变。结肠是丙酰-L-肉碱释放和吸收的主要部位。单次给予500或1000 mg丙酰-L-肉碱后，血浆丙酰-L-肉碱和L-肉碱浓度相比基线分别升高至2.6倍和1.2 - 1.3倍。连续7天每天两次给予500和1000 mg多剂量，相对于单剂量给药后达到的浓度，并未显著提高丙酰-L-肉碱或L-肉碱的最大血浆浓度。结肠是MMX-丙酰-L-肉碱片剂中丙酰-L-肉碱释放和吸收的主要部位。每天两次给予500 mg至1000 mg丙酰-L-肉碱的剂量耐受性良好，这为进一步研究评估MMX-丙酰-L-肉碱制剂在远端胃肠道疾病患者中的疗效提供了依据。
