吗啡的临床药代动力学。

文章的细节

引用

复制到剪贴板

眩光PA，沃尔什TD

吗啡的临床药代动力学。

《药物监测》1991年1月;13(1):1-23。

PubMed ID

2057987 (PubMed视图

］

摘要

吗啡(M)被世界卫生组织推荐为中重度癌症疼痛的治疗选择。在过去的20年里，灵敏放射免疫分析(RIA)和高效液相色谱法的发展使得对M的药代动力学的研究成为可能，这一点仍然不完全了解。由于代谢物与抗血清的交叉反应，RIA得到的数据必须谨慎解释，这会损害分析的特异性。M的药代动力学已经确定了各种临床情况，但大多数参数在患者之间存在很大的变异性。除透皮给药外，M易于从所有给药途径吸收，并可经脊髓注射。肌注和皮下给药后15-20分钟内达到血浆峰值，口服后30-90分钟内达到峰值。口服给药后的峰值水平远低于肠外途径，因为口服M在肝脏中经历了广泛的首过代谢。经反复给药，口服-肠外相对效价比为1:3 M可硬膜外或鞘内给药，也可脑室内给药。硬膜外M进入蛛网膜下腔，但也被体循环吸收。只有5%的剂量穿过硬脑膜。 M administered in the lumbar region is quickly redistributed in the cerebrospinal fluid in a rostral direction, explaining the high incidence of systemic side effects following spinal administration. After absorption, M is rapidly and widely distributed and crosses the blood-brain barrier. With therapeutic doses, plasma protein binding is only 20-35%, and the volume of distribution is 1-6 L/kg. The primary site of M metabolism is the liver, and the dose should be reduced in patients with liver disease. Glucuronidation is the main metabolic pathway, but the principal metabolite, morphine-3-glucuronide (M3G), is inactive. Morphine-6-glucuronide (M6G) is produced in smaller amounts than M3G, but is pharmacologically active and many times more potent than M. The ratio of M6G to M in plasma, after a dose of M, is approximately 10:1, and the ratio does not change with increasing doses or prolonged treatment. Normorphine (NM) is also active, and is formed to a greater extent after oral administration; it is not, however, usually found in plasma. NM may be neurotoxic. M and its metabolites are excreted by the kidney, but urinary free M accounts for less than 10% of an administered dose. In patients with renal insufficiency, the metabolites accumulate, though M itself is still excreted.(ABSTRACT TRUNCATED AT 400 WORDS)

引用本文的药物库数据

药物

吗啡