Yamamoto Yuki, Masuda Satohiro, Nakase Hiroshi, Matsuura Minoru, Maruyama Shihoko, Hisamatsu Tadakazu, Suzuki Yasuo, Matsubara Kazuo
Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital.
Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University.
Biol Pharm Bull. 2019 Jan 1;42(1):81-86. doi: 10.1248/bpb.b18-00561. Epub 2018 Oct 24.
The efficacy of 5-aminosalicylic acid (5-ASA) as the first-line therapy for ulcerative colitis (UC) is determined by the extent of drug delivery to the inflamed region. Moreover, differences among the various formulations influence delivery of the drug. In this study, we examined the clinical significance of colonic mucosal concentrations of 5-ASA and N-acetylmesalamine (Ac-5-ASA) in UC patients receiving a pH-dependent or time-dependent release formulation of 5-ASA. The subjects were 67 patients with UC who were treated with a pH-dependent or time-dependent formulation of 5-ASA between December 2011 and April 2014. A retrospective observational analysis of clinical outcomes was performed using the clinical activity index (CAI) obtained on the day of biopsy. Colonic mucosal concentrations of 5-ASA and Ac-5-ASA in biopsy samples were measured by LC-tandem mass spectrometry/mass spectrometry. Patients who were treated with the pH-dependent formulation had higher colon mucosal concentrations of 5-ASA than those who were treated with the time-dependent formulation. Additionally, 5-ASA concentration was significantly higher in patients with CAI scores ≤3. A higher concentration of Ac-5-ASA was achieved with the time-dependent formulation than with the pH-dependent formulation. Furthermore, patients with CAI scores ≤3 had higher concentrations of 5-ASA than those with CAI scores ≥4. The colonic mucosal concentration of 5-ASA in patients with UC is influenced by the pharmaceutical formulation and the remission status of UC.
5-氨基水杨酸（5-ASA）作为溃疡性结肠炎（UC）一线治疗药物的疗效取决于药物向炎症区域的递送程度。此外，不同制剂之间的差异会影响药物的递送。在本研究中，我们研究了接受pH依赖性或时间依赖性释放制剂5-ASA的UC患者结肠黏膜中5-ASA和N-乙酰美沙拉嗪（Ac-5-ASA）浓度的临床意义。研究对象为67例UC患者，他们在2011年12月至2014年4月期间接受了pH依赖性或时间依赖性制剂5-ASA的治疗。使用活检当天获得的临床活动指数（CAI）对临床结局进行回顾性观察分析。通过液相色谱-串联质谱法测量活检样本中5-ASA和Ac-5-ASA的结肠黏膜浓度。接受pH依赖性制剂治疗的患者结肠黏膜中5-ASA的浓度高于接受时间依赖性制剂治疗的患者。此外，CAI评分≤3的患者中5-ASA浓度显著更高。时间依赖性制剂比pH依赖性制剂能达到更高的Ac-5-ASA浓度。此外，CAI评分≤3的患者5-ASA浓度高于CAI评分≥4的患者。UC患者结肠黏膜中5-ASA的浓度受药物制剂和UC缓解状态影响。
