Shimizu Toshiaki, Nakayama Yoshiko, Ishii Eizaburo, Ida Shinobu, Satou Tomoki, Tokuhara Daisuke, Arai Katsuhiro, Nii Masahiro, Rydholm Hans, Yajima Toshitaka
Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Matsumoto, Nagano, Japan.
Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
Pediatr Int. 2019 Jan;61(1):87-95. doi: 10.1111/ped.13733.
Proton pump inhibitors (PPI) are widely used for the treatment of gastric acid-related disease, but they are not approved for use in children in Japan. To assess the safety, pharmacokinetics, pharmacodynamics, and efficacy (gastrointestinal symptom improvement) of PPI in Japanese pediatric patients with gastric acid-related disease, we conducted an 8 week, open-label, parallel-group, multicenter, phase I/III study of once-daily oral esomeprazole use.
Japanese children, aged 1-14 years with gastric acid-related disease, were stratified by weight and age into five groups (10 patients/group) to receive esomeprazole as granules for suspension (10 mg) or capsules (10 mg or 20 mg) once daily.
Esomeprazole was absorbed and eliminated rapidly in all groups, with a median time to reach maximum plasma concentration of 1.47-1.75 h, an arithmetic mean terminal elimination half-life of 0.80-1.37 h, and a weight-correlated apparent total body clearance of 0.216-0.343 L/h/kg. Area under the plasma concentration-time curve during a dosage interval and maximum plasma drug concentration were generally higher in groups given a higher dose (20 mg) or with a lower age/weight, but also in patients identified as poor metabolizers on cytochrome P450 2C19 genotype. Most patients who had any upper gastrointestinal symptoms at baseline were asymptomatic at the end of the study. Thirty-three patients (66%) reported ≥1 adverse events, including three patients who reported serious adverse events not judged to be causally related to esomeprazole.
Oral esomeprazole, at 10 mg or 20 mg once daily, had a similar safety, efficacy, and pharmacokinetic profile in Japanese pediatric patients to that previously seen in adults and Caucasian children.
质子泵抑制剂（PPI）广泛用于治疗胃酸相关疾病，但在日本未被批准用于儿童。为评估PPI在日本患有胃酸相关疾病的儿科患者中的安全性、药代动力学、药效学及疗效（胃肠道症状改善情况），我们开展了一项为期8周的开放标签、平行组、多中心I/III期研究，每日一次口服埃索美拉唑。
将1至14岁患有胃酸相关疾病的日本儿童按体重和年龄分层为五组（每组10例患者），每日一次接受埃索美拉唑混悬颗粒（10mg）或胶囊（10mg或20mg）治疗。
埃索美拉唑在所有组中吸收和消除迅速，达到最大血浆浓度的中位时间为1.47 - 1.75小时，算术平均终末消除半衰期为0.80 - 1.37小时，体重相关的表观全身清除率为0.216 - 0.343升/小时/千克。给药间隔期间血浆浓度 - 时间曲线下面积和最大血浆药物浓度在给予较高剂量（20mg）或年龄/体重较低的组中通常较高，在细胞色素P450 2C19基因型被鉴定为代谢不良的患者中也是如此。大多数在基线时有任何上消化道症状的患者在研究结束时无症状。33例患者（66%）报告了≥1次不良事件，其中3例患者报告了被判定与埃索美拉唑无因果关系的严重不良事件。
每日一次口服10mg或20mg埃索美拉唑，在日本儿科患者中的安全性、疗效和药代动力学特征与先前在成人和白种儿童中所见相似。
