Petrone D, Kamin M, Olson W
Arthritis Centers of Texas, Dallas 75246, USA.
J Clin Pharm Ther. 1999 Apr;24(2):115-23. doi: 10.1046/j.1365-2710.1999.00203.x.
Ultram [tramadol hydrochloride (HCl)] is a centrally acting analgesic that is widely prescribed for the treatment of moderate to moderately severe chronic pain. Although tramadol is generally well tolerated, some patients discontinue use early in the course of treatment because of nausea and vomiting.
To investigate the effect of three initial titration rates of tramadol HCl on the incidence of discontinuation due to nausea and/or vomiting in patients who previously did not tolerate tramadol HCl.
A multicentre, outpatient, randomized double-blind study was conducted, comprised of two phases: a 14-day open-label run-in phase and a 28-day double-blind phase. In the run-in phase the dose of tramadol was titrated over 4 days to the target of 200 mg/day. Patients who discontinued tramadol HCl due to nausea and/or vomiting in the open-label phase were eligible to enter the 28-day double-blind phase after a 10-day wash-out. Patients were randomized to one of three groups using a 10-, 16- or a 13-day titration schedule in order to achieve a target dosage of either 200 mg/day (10- and 16-day titration groups) or 150 mg/day (13-day titration group). The number of discontinuations due to nausea and/or vomiting in each group were compared.
Significantly fewer patients (22%) discontinued because of nausea and/or vomiting in the 13- and 16-day titration groups compared to the 10-day group (P=0.008 and P=0.006, respectively). The time to discontinuation was also significantly delayed in the 13- and 16-day groups compared to the 10-day group (P=0.006 and P=0.007, respectively). The outcome of the 13-day titration to 150 mg/day was essentially the same as that of the 16-day titration to 200 mg/day, suggesting that this is a true rate effect rather than being dose related.
This study demonstrated that a slower titration rate of tramadol HCl improves tolerability in patients who previously discontinued therapy due to nausea and/or vomiting. This study also demonstrates that the rate of titration of tramadol HCl rather than the target dose is the major determinant of tolerability.
曲马多[盐酸曲马多（HCl）]是一种中枢性镇痛药，广泛用于治疗中度至中度重度慢性疼痛。尽管曲马多通常耐受性良好，但一些患者在治疗过程早期因恶心和呕吐而停药。
研究盐酸曲马多三种初始滴定速率对既往不耐受盐酸曲马多患者因恶心和/或呕吐导致停药发生率的影响。
进行了一项多中心、门诊、随机双盲研究，包括两个阶段：14天的开放标签导入期和28天的双盲期。在导入期，曲马多剂量在4天内滴定至200毫克/天的目标剂量。在开放标签期因恶心和/或呕吐停用盐酸曲马多的患者，在10天洗脱期后有资格进入28天双盲期。患者使用10天、16天或13天的滴定方案随机分为三组，以达到200毫克/天（10天和16天滴定组）或150毫克/天（13天滴定组）的目标剂量。比较每组因恶心和/或呕吐导致的停药次数。
与10天组相比，13天和16天滴定组因恶心和/或呕吐停药的患者明显较少（分别为22%）（P = 0.008和P = 0.006）。与10天组相比，13天和16天组的停药时间也明显延迟（分别为P = 0.006和P = 0.007）。13天滴定至150毫克/天的结果与16天滴定至200毫克/天的结果基本相同，表明这是一种真正的速率效应，而非剂量相关。
本研究表明，盐酸曲马多较慢的滴定速率可提高既往因恶心和/或呕吐而停药患者的耐受性。本研究还表明，盐酸曲马多的滴定速率而非目标剂量是耐受性的主要决定因素。
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