glycyl=>glycyl=>leucyl=>glycyl=>glycine | 7325-25-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: glycyl=>glycyl=>leucyl=>glycyl=>glycine
• 英文别名: N-{N-[N-(N-Glycyl-glycyl)-leucyl]-glycyl}-glycin；Diglycyl-leucyl-glycyl-glycin；Glycyl=>glycyl=>leucyl=>glycyl=>glycin；2-[[2-[[2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-4-methylpentanoyl]amino]acetyl]amino]acetic acid
• CAS: 7325-25-9
• 化学式: C₁₄H₂₅N₅O₆
• 分子量: 359.382
• InChiKey: LHRMJYHUIJNAJJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.09
• 重原子数：
  25.0
• 可旋转键数：
  11.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  179.72
• 氢给体数：
  6.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  DL-亮氨酰-甘氨酰-甘氨酸 在 sodium hydroxide 、 氨 、 水 作用下， 生成 glycyl=>glycyl=>leucyl=>glycyl=>glycine
  参考文献：
  名称：

  Evaluation of the bioequivalence of tablets and capsules containing the novel anticancer agent R115777 (Zarnestra) in patients with advanced solid tumors

  摘要：

  R115777 (Zamestra) is a novel anticancer agent, currently undergoing phase III clinical testing. An open, cross-over trial was performed in 24 patients with solid tumors to compare the bioavailability of a new tablet formulation with the standard capsule formulation. Both dosage forms were administered once daily in doses of 300 or 400 mg. Patients received R 115777 as a capsule on day I and as a tablet on day 2, or vice versa. Blood samples were drawn up to 24 hours after drug intake and R 115777 levels were measured using a validated high performance liquid chromatography (HPLC) method. The following pharmacokinetic parameters were determined and compared for the two formulations: time to maximal plasma concentration (T-max), half-life (t(1/2)), maximal plasma concentration (C-max) and area under the curve at twenty-four hours (AUC(24h)). For the latter two parameters, 90% classical confidence intervals of the ratio tablet/capsule were calculated after a log-transformation, using an Analysis of Variance (ANOVA). For t(1/2) and T-max, no statistically significant differences were found between tablet and capsule. The point estimates of the ratio's of the log-normalized C-max and AUC(24h) were 0.94 and 0.92, respectively, and the 90% confidence intervals were 0.81-1.09 and 0.83-1.03, which is within the critical range for bioequivalence of 0.80-1.25. In conclusion, the established pharmacokinetic parameters demonstrate that the capsule and tablet formulations of R 115777 are interchangeable.

  DOI：

  10.1007/bf03190407

文献信息

• Evaluation of the bioequivalence of tablets and capsules containing the novel anticancer agent R115777 (Zarnestra) in patients with advanced solid tumors
  作者：M. Crul、G. J. De Klerk、M. Swart、L. Weiner、P. A. Palmer、C. J. Bol、J. H. Beijnen、J. H. M. Schellens

  DOI：10.1007/bf03190407

  日期：2002.3

  R115777 (Zamestra) is a novel anticancer agent, currently undergoing phase III clinical testing. An open, cross-over trial was performed in 24 patients with solid tumors to compare the bioavailability of a new tablet formulation with the standard capsule formulation. Both dosage forms were administered once daily in doses of 300 or 400 mg. Patients received R 115777 as a capsule on day I and as a tablet on day 2, or vice versa. Blood samples were drawn up to 24 hours after drug intake and R 115777 levels were measured using a validated high performance liquid chromatography (HPLC) method. The following pharmacokinetic parameters were determined and compared for the two formulations: time to maximal plasma concentration (T-max), half-life (t(1/2)), maximal plasma concentration (C-max) and area under the curve at twenty-four hours (AUC(24h)). For the latter two parameters, 90% classical confidence intervals of the ratio tablet/capsule were calculated after a log-transformation, using an Analysis of Variance (ANOVA). For t(1/2) and T-max, no statistically significant differences were found between tablet and capsule. The point estimates of the ratio's of the log-normalized C-max and AUC(24h) were 0.94 and 0.92, respectively, and the 90% confidence intervals were 0.81-1.09 and 0.83-1.03, which is within the critical range for bioequivalence of 0.80-1.25. In conclusion, the established pharmacokinetic parameters demonstrate that the capsule and tablet formulations of R 115777 are interchangeable.