可待因在单剂量和慢性剂量后在一种低剂量和七种广泛代谢物中的分布和代谢。
文章的细节
-
引用
复制到剪贴板 -
陈志荣，陈志强，陈志强，陈志强
可待因在单剂量和慢性剂量后在一种低剂量和七种广泛代谢物中的分布和代谢。
临床药物学杂志，1991 04;31(4):381-90。
- PubMed ID
-
2049245 (PubMed视图］
- 摘要
-
1.在8名受试者(7名右美沙芬大量代谢者和1名右美沙芬低代谢者)中，研究了单次(30 mg)和慢性(30 mg 8小时，7次)给药后，可待因对吗啡、去甲可待因和可待因-6-葡萄糖苷的药代动力学、代谢和部分清除率。用高效液相色谱法测定可待因、可待因-6-葡萄糖苷、吗啡和去可待因的含量。2.单次给药后，达到血浆可待因最高浓度的时间为0.97 +/- 0.31 h(平均+/- s.d)，而可待因-6-葡萄糖苷达到最大浓度的时间为1.28 +/- 0.49 h。可待因-6-葡萄糖苷的血浆AUC是可待因的15.8 +/- 4.5倍。唾液中可待因的AUC是血浆中的3.4 +/- 1.1倍。可待因的消除半衰期为3.2 +/- 0.3 h，可待因-6-葡萄糖苷的消除半衰期为3.2 +/- 0.9 h。可待因的肾脏清除率为183 +/- 59 ml min-1，与尿液pH值呈负相关(r = 0.81)。这些数据表明可待因在肾小球滤过、肾小管分泌和被动再吸收。可待因-6-葡萄糖苷的肾脏清除率为55 +/- 21 ml min-1，与尿液ph无关。其与人血浆的结合小于10%。 These data suggest that codeine-6-glucuronide undergoes filtration at the glomerulus and tubular reabsorption. This latter process is unlikely to be passive. 4. After chronic dosing, the pharmacokinetics of codeine and codeine-6-glucuronide were not significantly different from the single dose pharmacokinetics. 5. After the single dose, 86.1 +/- 11.4% of the dose was recovered in urine, of which 59.8 +/- 10.3% was codeine-6-glucuronide, 7.1 +/- 1.1% was total morphine, 6.9 +/- 2.1% was total norcodeine and 11.8 +/- 3.9% was unchanged codeine. These recoveries were not significantly different (P greater than 0.05) after chronic administration. 6. After the single dose, the partial clearance to morphine was 137 +/- 31 ml min-1 in the seven extensive metabolisers and 8 ml min-1 in the poor metaboliser; to norcodeine the values were 103 +/- 33 ml min-1 and 90 ml min-1; to codeine-6-glucuronide the values were 914 +/- 129 ml min-1 and 971 ml min-1; and intrinsic clearance was 1568 +/- 103 ml min-1 and 1450 ml min-1. These values were not significantly (P greater than 0.05) altered by chronic administration.(ABSTRACT TRUNCATED AT 400 WORDS)
引用本文的药物库数据
- 药物