1-[2H3,13C]methylxanthine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 1-[2H3,13C]methylxanthine
• 英文别名: 1-Methylxanthine-13C,d3；1-(trideuterio(113C)methyl)-3,7-dihydropurine-2,6-dione
• 化学式: C₆H₆N₄O₂
• 分子量: 170.104
• InChiKey: MVOYJPOZRLFTCP-KQORAOOSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  78.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  碘甲烷-13C,d3 、 黄嘌呤 在 sodium hydroxide 作用下， 反应 24.0h， 生成 1-[2H3,13C]methylxanthine
  参考文献：
  名称：

  Fluvoxamine–theophylline interaction: Gap between in vitro and in vivo inhibition constants toward cytochrome P4501A2

  摘要：

  Objective: Several reports indicate that fluvoxamine decreases the clearance of cytochrome P4501A2 (CYP1A-2) substrates. This study compared in vitro and in vivo inhibition potencies of fluvoxamine toward CYP1A2 with an approach based on inhibition constants (K-i) determined in vitro and in vivo.Methods: In vitro inhibition constant values were determined with human liver microsomes and complementary deoxyribonucleic acid-expressed CYP1A2 (supersomes). Fluvoxamine in vivo inhibition constants (K(i)iv) for CYP1A2 were obtained from an investigation of single-dose theophylline (250 mg) disposition in 9 healthy volunteers receiving steady-state (9 days) fluvoxamine at 3 doses (0, 25, or 75 mg/d) in a randomized crossover design.Results: In vitro K-i values based on total inhibitor concentrations were 177 +/- 56 nmol/L, 121 +/- 21 nmol/L, and 52 +/- 13 nmol/L in human liver microsomes with 1 mg/ml protein and 0.5 mg/ml protein and in supersomes with 0.3 mg/ml protein, respectively. The corresponding in vitro K-i values based on unbound fluvoxamine concentrations were 35 nmol/L, 36 nmol/L, and 36 nmol/L. The ratio of 1-methyluric acid formation clearances (control/inhibited) in 8 subjects was positively correlated with fluvoxamine concentration (r(2) = 0.87; P < .001) with an intercept near 1. Mean values for K(i)iv based on total and unbound plasma concentrations at steady state were 25.3 nmol/L (range, 14-39 nmol/L) and 3.6 nmol/L (range, 2.4-5.9 nmol/L), respectively.Conclusion: Comparison of in vitro and in vivo K-i values based on unbound fluvoxamine concentrations suggests that fluvoxamine inhibition potency is approximately 10 times greater in vivo than in vitro.

  DOI：

  10.1067/mcp.2001.119724

文献信息

• Fluvoxamine–theophylline interaction: Gap between in vitro and in vivo inhibition constants toward cytochrome P4501A2
  作者：C Yao

  DOI：10.1067/mcp.2001.119724

  日期：2001.11

  Objective: Several reports indicate that fluvoxamine decreases the clearance of cytochrome P4501A2 (CYP1A-2) substrates. This study compared in vitro and in vivo inhibition potencies of fluvoxamine toward CYP1A2 with an approach based on inhibition constants (K-i) determined in vitro and in vivo.Methods: In vitro inhibition constant values were determined with human liver microsomes and complementary deoxyribonucleic acid-expressed CYP1A2 (supersomes). Fluvoxamine in vivo inhibition constants (K(i)iv) for CYP1A2 were obtained from an investigation of single-dose theophylline (250 mg) disposition in 9 healthy volunteers receiving steady-state (9 days) fluvoxamine at 3 doses (0, 25, or 75 mg/d) in a randomized crossover design.Results: In vitro K-i values based on total inhibitor concentrations were 177 +/- 56 nmol/L, 121 +/- 21 nmol/L, and 52 +/- 13 nmol/L in human liver microsomes with 1 mg/ml protein and 0.5 mg/ml protein and in supersomes with 0.3 mg/ml protein, respectively. The corresponding in vitro K-i values based on unbound fluvoxamine concentrations were 35 nmol/L, 36 nmol/L, and 36 nmol/L. The ratio of 1-methyluric acid formation clearances (control/inhibited) in 8 subjects was positively correlated with fluvoxamine concentration (r(2) = 0.87; P < .001) with an intercept near 1. Mean values for K(i)iv based on total and unbound plasma concentrations at steady state were 25.3 nmol/L (range, 14-39 nmol/L) and 3.6 nmol/L (range, 2.4-5.9 nmol/L), respectively.Conclusion: Comparison of in vitro and in vivo K-i values based on unbound fluvoxamine concentrations suggests that fluvoxamine inhibition potency is approximately 10 times greater in vivo than in vitro.