Formerly Covance Clinical Research Unit Ltd, Leeds, UK.
Formerly Pharmaceutical Profiles Ltd, Ruddington, UK.
Pharmacol Res Perspect. 2022 Jun;10(3):e00957. doi: 10.1002/prp2.957.
Patients with osteoporosis often take oral bisphosphonates with food, rendering these medications ineffective. This study compared the relative absorption of four formulations of gastro-resistant (GR; formulations 1-4) risedronate 35 mg versus immediate-release (IR) risedronate 35 mg taken fasted. Secondarily, it compared the relative absorption of GR formulations administered fed and fasted, and determined the site of disintegration. Healthy participants (N = 160) were randomized to one of nine treatment groups: IR risedronate taken fasted (group A) or formulations 1-4 taken fasted or fed (groups B-I). Fasted groups fasted for 8 h pre-dose and 4 h post-dose. Fed groups fasted for 7.5 h, then took risedronate with breakfast. Urine was collected until 72 h post-dose and analyzed using liquid chromatography. From each group, up to seven participants underwent scintigraphic monitoring to assess tablet disintegration. The percentage of total dose recovered in urine (A' ) was ~0.5% for group A. The A' of formulations 1-4 taken fasted was 0.220% (90% confidence interval 0.124-0.389), 0.298% (0.122-0.730), 0.154% (0.090-0.264), and 0.108% (0.051-0.231), respectively. With food, the A' of formulation 1 decreased least versus fasted (-27%) compared with the A' of formulations 2, 3, and 4 (-73%, -80%, and -65%, respectively). Formulations 1-3 disintegrated in the small intestine, formulation 4 closer to the large intestine. All GR formulations were well tolerated and in line with the known safety profile for IR risedronate. Formulation 2 had the highest absorption when taken fasted, whereas the absorption of formulation 1 was least affected by food.
骨质疏松症患者常随餐服用口服双膦酸盐类药物，导致这些药物疗效降低。本研究比较了四种胃溶型（GR；配方 1-4）利塞膦酸钠 35mg 与空腹服用的即释（IR）利塞膦酸钠 35mg 的相对吸收情况。其次，还比较了这些 GR 配方在空腹和进食时的相对吸收情况，并确定了崩解部位。将 160 名健康参与者随机分为九组中的一组：空腹服用 IR 利塞膦酸钠（A 组）或空腹或进食时服用配方 1-4（B-I 组）。空腹组在给药前禁食 8 小时，给药后禁食 4 小时。进食组禁食 7.5 小时，然后随早餐服用利塞膦酸钠。给药后 72 小时内收集尿液，并采用液相色谱法进行分析。从每组中，最多有 7 名参与者接受闪烁扫描监测，以评估片剂崩解情况。A 组中，尿液中总剂量的回收百分比（A'）约为 0.5%。空腹服用配方 1-4 的 A'分别为 0.220%（90%置信区间 0.124-0.389）、0.298%（0.122-0.730）、0.154%（0.090-0.264）和 0.108%（0.051-0.231）。与食物同服时，配方 1 的 A'下降最少（与空腹相比减少 27%），而配方 2、3 和 4 的 A'分别下降 73%、80%和 65%。配方 1-3 在小肠中崩解，配方 4 更接近大肠。所有 GR 配方均具有良好的耐受性，与 IR 利塞膦酸钠已知的安全性概况一致。配方 2 空腹服用时吸收最高，而配方 1 的吸收受食物影响最小。
