Paulsen O, Nilsson L G, Saint-Salvi B, Manuel C, Lunell E
Department of Clinical Pharmacology, University Hospital, Lund, Sweden.
Pharmacol Toxicol. 1988 Oct;63(4):215-20. doi: 10.1111/j.1600-0773.1988.tb00943.x.
The macrolide antibiotics are metabolized by cytochrome P-450 enzymes in the liver and interactions with similarly metabolized compounds have been described. Simultaneous treatment with erythromycin and warfarin is known to decrease warfarin clearance and prolong prothrombin time. Roxithromycin (RU 28965), a new erythromycin derivative with improved pharmacokinetic properties, might then, because of structure similarity, be expected to interact with warfarin. In 21 healthy volunteers, the effect of orally administered roxithromycin (150 mg b.i.d.) on warfarin steady-state kinetics, and the effects of warfarin on roxithromycin kinetics, were investigated in a double-blind, randomized study versus placebo. Since the warfarin enantiomers, R- and S-warfarin have both different potency and different metabolism, the ratio between the enantiomers with and without roxithromycin, was also determined. In this study, mean AUC for warfarin increased slightly from day 14 of warfarin treatment to day 28, but no difference was found between the roxithromycin group and the placebo group, and no change appeared in the ratio between the warfarin enantiomers. A moderate increase in dosage was needed to maintain hypocoagulability during warfarin medication, but there was no difference between the roxithromycin group and the placebo groups, respectively. In addition, roxithromycin kinetics appeared to be unaffected by warfarin treatment.
大环内酯类抗生素在肝脏中由细胞色素P - 450酶代谢，并且已报道其与同样经此代谢的化合物存在相互作用。已知同时使用红霉素和华法林会降低华法林的清除率并延长凝血酶原时间。罗红霉素（RU 28965）是一种具有改善药代动力学性质的新型红霉素衍生物，由于结构相似，因此可能会与华法林发生相互作用。在一项双盲、随机、与安慰剂对照的研究中，对21名健康志愿者口服罗红霉素（150毫克，每日两次）对华法林稳态动力学的影响以及华法林对罗红霉素动力学的影响进行了研究。由于华法林对映体R - 华法林和S - 华法林具有不同的效能和不同的代谢方式，因此还测定了服用罗红霉素和未服用罗红霉素时对映体之间的比例。在本研究中，华法林的平均AUC从华法林治疗第14天到第28天略有增加，但罗红霉素组和安慰剂组之间未发现差异，并且华法林对映体之间的比例也没有变化。在华法林用药期间需要适度增加剂量以维持低凝状态，但罗红霉素组和安慰剂组之间分别没有差异。此外，罗红霉素的动力学似乎不受华法林治疗的影响。
