静脉注射地尔硫䓬与CYP3A介导的代谢
Intravenous diltiazem and CYP3A-mediated metabolism.
作者信息
Masica A L, Azie N E, Brater D C, Hall S D, Jones D R
机构信息
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Wishard Memorial Hospital, OPW 320, 1001 West 10th Street, Indianapolis, IN 46202, USA.
出版信息
Br J Clin Pharmacol. 2000 Sep;50(3):273-6. doi: 10.1046/j.1365-2125.2000.00249.x.
AIMS
To study whether intravenous diltiazem, a calcium channel blocker commonly prescribed for hypertension and stable angina, is an inhibitor of the CYP3A enzymes by using oral lovastatin, an HMG Co-A reductase inhibitor, as a substrate.
METHODS
Ten healthy volunteers were studied in a randomized two-way crossover design. The two arms were 1) administration of a 20 mg dosage of lovastatin orally and 2) administration of a 20 mg dosage of lovastatin orally 1 h after an intravenous loading dosage and constant infusion of diltiazem. Blood samples were collected up to 25 h in order to quantify lovastatin and diltiazem concentrations in the separated serum. Lovastatin and diltiazem concentrations were quantified by GC-MS and h.p.l.c., respectively.
RESULTS
Intravenous diltiazem did not significantly affect the oral AUC, Cmax, t(1/2), or tmax of lovastatin.
CONCLUSIONS
These data suggest that the interaction of lovastatin with diltiazem does not occur systemically and is primarily a first-pass effect. Thus, drug interactions with diltiazem may become evident when a patient is moved from intravenous to oral dosing.
目的
以口服HMG Co - A还原酶抑制剂洛伐他汀作为底物，研究常用于治疗高血压和稳定型心绞痛的钙通道阻滞剂静脉注射地尔硫䓬是否为CYP3A酶的抑制剂。
方法
采用随机双向交叉设计对10名健康志愿者进行研究。两组分别为：1）口服20mg剂量的洛伐他汀；2）静脉注射负荷剂量并持续输注地尔硫䓬1小时后口服20mg剂量的洛伐他汀。采集血样长达25小时，以定量分离血清中洛伐他汀和地尔硫䓬的浓度。洛伐他汀和地尔硫䓬的浓度分别通过气相色谱 - 质谱联用仪（GC - MS）和高效液相色谱法（h.p.l.c.）进行定量分析。
结果
静脉注射地尔硫䓬对洛伐他汀的口服药时曲线下面积（AUC）、最大血药浓度（Cmax）、半衰期（t(1/2)）或达峰时间（tmax）均无显著影响。
结论
这些数据表明，洛伐他汀与地尔硫䓬之间的相互作用并非全身性的，主要是首过效应。因此，当患者从静脉给药转为口服给药时，与地尔硫䓬的药物相互作用可能会变得明显。
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