Koehntop D E, Noormohamed S E, Fletcher C V
Department of Anesthesiology, University of Minnesota Hospital and Clinic, Minneapolis 55455.
Pharmacotherapy. 1994 Sep-Oct;14(5):592-9.
Although patients in renal failure frequently take several drugs on a long-term basis, drug-induced alterations in alfentanil metabolism have not been examined as a possible source of variability in alfentanil clearance in this population. We compared the pharmacokinetics of alfentanil during renal transplantation in seven patients receiving and six not receiving long-term drug therapy. After the rapid intravenous injection of alfentanil 100 micrograms/kg during isoflurane anesthesia, plasma concentrations were measured at intervals up to 6 hours by radioimmunoassay. The terminal elimination half-life, steady-state volume of distribution (Vdss), and total body clearance were determined by noncompartmental methods. There was no statistical difference in the Vdss between the two patient groups. However, clearance was significantly higher and elimination half-life lower in the group taking long-term drugs: clearance 6.94 +/- 4.64 versus 3.47 +/- 0.16 ml.kg-1.min-1, and elimination half-life 50.6 +/- 13.9 versus 90.7 +/- 22.4 minutes, respectively (p < 0.05). The higher clearance occurred even though five of the seven patients were taking agents known to be metabolized by the same cytochrome P-450 hepatic isozyme that metabolizes alfentanil and therefore potential competitive inhibitors of alfentanil metabolism. Drugs taken by the three patients with the highest alfentanil clearances included known inducers of hepatic drug metabolism. Thus, in the presence of several long-term drugs, the clearance of alfentanil appears to be noticeably increased by inducers of hepatic drug metabolism but unaffected by potential competitive inhibitors.
尽管肾衰竭患者经常长期服用多种药物，但尚未研究药物引起的阿芬太尼代谢改变是否是该人群中阿芬太尼清除率变异性的可能来源。我们比较了7例接受长期药物治疗和6例未接受长期药物治疗的患者在肾移植期间阿芬太尼的药代动力学。在异氟烷麻醉期间快速静脉注射100微克/千克阿芬太尼后，通过放射免疫分析法每隔一段时间测量血浆浓度，直至6小时。通过非房室方法确定终末消除半衰期、稳态分布容积（Vdss）和全身清除率。两组患者的Vdss无统计学差异。然而，长期服药组的清除率显著更高，消除半衰期更低：清除率分别为6.94±4.64和3.47±0.16毫升·千克-1·分钟-1，消除半衰期分别为50.6±13.9和90.7±22.4分钟（p<0.05）。即使7例患者中有5例服用的药物已知由与代谢阿芬太尼相同的细胞色素P-450肝同工酶代谢，因此可能是阿芬太尼代谢的竞争性抑制剂，但清除率仍较高。阿芬太尼清除率最高的3例患者所服用的药物包括已知的肝药代谢诱导剂。因此，在存在多种长期药物的情况下，阿芬太尼的清除率似乎因肝药代谢诱导剂而显著增加，但不受潜在竞争性抑制剂的影响。
