Blyden G T, Scavone J M, Greenblatt D J
Department of Psychiatry, Tufts University School of Medicine, Boston, Massachusetts.
J Clin Pharmacol. 1988 Mar;28(3):240-5. doi: 10.1002/j.1552-4604.1988.tb03139.x.
Healthy volunteers received single doses of either phenytoin (300 mg IV), alprazolam (1 mg orally) or lorazepam (2 mg IV) on two occasions in random sequence. One of the two trials was a control; for the other trial, subjects ingested metronidazole, 250 mg three times daily beginning 4 days prior to and continuing for the duration of each kinetic study. Compared with control, metronidazole significantly prolonged phenytoin half-life (23 versus 16 hours, P less than .02) and reduced its clearance (.28 versus .33 mL/min/kg, P less than .005), known to depend on aromatic hydroxylation. However, metronidazole did not significantly alter kinetic variables for either alprazolam (metabolized by aliphatic hydroxylation) or lorazepam (metabolized by glucuronide conjugation). Thus, metronidazole has the capacity to impair the clearance of certain oxidatively metabolized drugs, but there is no apparent way to predict which drugs will be so influenced.
健康志愿者分两次随机接受单剂量的苯妥英（静脉注射300毫克）、阿普唑仑（口服1毫克）或劳拉西泮（静脉注射2毫克）。两项试验中的一项为对照试验；在另一项试验中，受试者从每次动力学研究前4天开始，每天3次服用250毫克甲硝唑，并持续整个动力学研究期间。与对照组相比，甲硝唑显著延长了苯妥英的半衰期（23小时对16小时，P小于0.02），并降低了其清除率（0.28对0.33毫升/分钟/千克，P小于0.005），已知其清除率取决于芳香族羟基化作用。然而，甲硝唑对阿普唑仑（通过脂肪族羟基化代谢）或劳拉西泮（通过葡萄糖醛酸结合代谢）的动力学变量没有显著影响。因此，甲硝唑有能力损害某些经氧化代谢药物的清除率，但没有明显的方法来预测哪些药物会受到如此影响。
