BACKGROUND & AIMS:
BACKGROUND:To date, no definitive treatment of functional dyspepsia (FD) has been proven to be effective and reasonably well-tolerated. Proton pump inhibitors (PPIs) combined with prokinetic agents are considered an effective option. Revaprazan is a selective potassium-competitive acid blocker that reversibly inhibits gastric H(+)/K(+)-ATPase and shows effective acid suppression comparable to PPIs. Itopride is a prokinetic agent that has anticholinesterase activity as well as dopamine D(2) receptor antagonistic activity. For this reason, revaprazan and itopride have been prescribed for FD; however, no available studies have reported the pharmacokinetic interactions of these 2 drugs.
OBJECTIVE:The objective of this study was to compare the bioavailability and tolerability of revaprazan and itopride combination therapy to those of equally dosed monotherapies to acquire basic drug-drug interaction information about revaprazan.
METHODS:This multiple-dose, randomized crossover study was conducted in healthy male Korean subjects. Subjects received, in randomized sequence, a 7-day oral dose of revaprazan 200 mg once daily, itopride 50 mg TID, or both. Each treatment period was separated by a 7-day washout period. Blood samples were collected for up to 24 hours following the last dose at steady state, and drug concentrations were determined using validated LC/MS-MS. Pharmacokinetic properties were obtained using noncompartmental analysis. Drug tolerability was assessed throughout the study, using measurements of vital signs, clinical chemistry testing, and interviews.
RESULTS:A total of 30 subjects were enrolled in the study. Among them, 28 subjects completed revaprazan treatment, and 27 completed the study (3 subjects were withdrawn). The geometric mean ratios (GMRs) (90% CI) of C(max,ss), and AUC(τ,ss) with revaprazan were 0.92 (0.84-1.00) and 0.96 (0.89-1.03), respectively. The GMRs of C(max,ss) and AUC(τ,ss) with itopride were 1.07 (0.96-1.20) and 1.12 (1.06-1.18), respectively. A total of 15 adverse events (AEs) were reported in 8 subjects. All AEs were considered to be mild, and there were no clinically significant differences between treatment groups.
CONCLUSION:The findings from this study suggest bioequivalence between revaprazan given as monotherapy and in combination with itopride in these healthy Korean male volunteers, with no clinical significant drug-drug interaction. All treatments in this study was generally well tolerated. ClinicalTrials.gov identifier: NCT0133289.
背景与目标:
背景:迄今为止,尚无权威的功能性消化不良(FD)治疗方法被证明是有效且耐受性良好的。质子泵抑制剂(PPI)与促动力剂结合被认为是有效的选择。 Revaprazan是一种选择性钾竞争性酸阻滞剂,可逆地抑制胃H()/ K()-ATPase,并显示出与PPI相当的有效酸抑制作用。依托必利是一种具有抗胆碱酯酶活性以及多巴胺D(2)受体拮抗活性的促动力剂。因此,已为FD规定了瑞伐拉赞和伊托必利。但是,尚无可用的研究报道这两种药物的药代动力学相互作用。
目的:本研究的目的是比较瑞伐拉赞和伊托必利联合疗法与等剂量单药疗法的生物利用度和耐受性,以获取有关瑞伐拉赞的基本药物相互作用信息。
方法:这项多剂量,随机交叉研究是在健康的韩国男性受试者中进行的。受试者随机接受7天口服瑞伐拉赞200毫克/天,伊托必利50毫克TID或两者兼有。每个治疗期间隔7天的清除期。在稳定状态下最后一次给药后长达24小时内收集血样,并使用经过验证的LC / MS-MS确定药物浓度。使用非房室分析获得药代动力学性质。在整个研究过程中,使用生命体征的测量,临床化学测试和访谈对药物耐受性进行了评估。
结果:总共30名受试者参加了该研究。其中,有28位受试者完成了瑞伐拉赞治疗,还有27位受试者完成了研究(退出了3位受试者)。 C(max,ss)和AUC(τ,ss)与瑞伐拉赞的几何平均比(GMR)(90%CI)分别为0.92(0.84-1.00)和0.96(0.89-1.03)。带有伊托必利的C(max,ss)和AUC(τ,ss)的GMR分别为1.07(0.96-1.20)和1.12(1.06-1.18)。在8位受试者中总共报告了15次不良事件(AE)。所有不良事件均被视为轻度,治疗组之间在临床上无显着差异。
结论:这项研究的结果表明,在这些健康的韩国男性志愿者中,瑞伐拉赞单药治疗与伊托必利联用具有生物等效性,且无临床上显着的药物相互作用。这项研究中的所有治疗方法一般都耐受良好。 ClinicalTrials.gov标识符:NCT0133289。