Bachmann K, Shapiro R, Fulton R, Carroll F T, Sullivan T J
Clin Pharmacol Ther. 1979 Mar;25(3):309-15. doi: 10.1002/cpt1979253309.
Nine cigarette smokers ingested an average daily 0.032 mg/kg dose of sodium warfarin for 2 wk while continuing to smoke and for an additional 2 wk after having abstained from cigarette smoking for a month washout phase. Steady-state plasma levels of warfarin, clearances, t 1/2, apparent volumes of distribution, steady-state prothrombin times, and plasma thiocyanate levels were measured during both the smoking and nonsmoking phases. During the nonsmoking phase there was a 13% increase in average steady-state warfarin level and a 13% decrease in warfarin clearance rate. There also was a 23% increase in warfarin t 1/2 and an 11% increase in the apparent volume of distribution. Prothrombin time did not change. Thiocyanate levels were 3 to 4 times as high during the smoking than the nonsmoking phase. It appears that cigarette smoking does affect warfarin clearance, t 1/2, and apparent volume of distribution, though the net effect on warfarin's pharmacodynamic activity is negligible, at least at doses which are ineffective therapeutically.
九名吸烟者在持续吸烟的情况下，平均每日摄入0.032毫克/千克剂量的华法林钠，持续2周，然后在经过一个月的戒烟洗脱期后又持续2周。在吸烟期和非吸烟期均测量了华法林的稳态血浆水平、清除率、半衰期、表观分布容积、稳态凝血酶原时间和血浆硫氰酸盐水平。在非吸烟期，华法林的平均稳态水平增加了13%，清除率降低了13%。华法林的半衰期也增加了23%，表观分布容积增加了11%。凝血酶原时间没有变化。吸烟期的硫氰酸盐水平是非吸烟期的3至4倍。看来吸烟确实会影响华法林的清除率、半衰期和表观分布容积，尽管对华法林药效学活性的净影响可以忽略不计，至少在治疗无效的剂量下是如此。
