Ansell Jack, McDonough Maryellen, Zhao Yanli, Harmatz Jerold S, Greenblatt David J
Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.
J Clin Pharmacol. 2009 Jul;49(7):824-30. doi: 10.1177/0091270009337510.
The question of potentiation of warfarin anticoagulation by cranberry juice (CJ) is a topic of biomedical importance. Anecdotal reports of CJ-warfarin interaction are largely unconfirmed in controlled studies. Thirty patients on stable warfarin anticoagulation (international normalized ratio [INR], 1.7-3.3) were randomized to receive 240 mL of CJ or 240 mL of placebo beverage, matched for color and taste, once daily for 2 weeks. The INR values and plasma levels of R- and S-warfarin were measured during the 2-week period and a 1-week follow-up period. The CJ and placebo groups (n=14 and 16, respectively) did not differ significantly in mean plasma R- and S-warfarin concentrations. Eight patients (4 on CJ, 4 on placebo) developed minimally elevated INR (range, 3.38-4.52) during the treatment period. Mean INR differed significantly (P<.02) only on treatment day 12; at all other time points, the groups did not differ. Cranberry juice has no effect on plasma S- or R-warfarin plasma levels, excluding a pharmacokinetic interaction. A small though statistically significant pharmacodynamic enhancement of INR by CJ at a single time point is unlikely to be clinically important and may be a random change. Enhanced warfarin anticoagulation attributed to CJ in anecdotal reports may represent a chance temporal association.
蔓越莓汁(CJ)增强华法林抗凝作用的问题是一个具有生物医学重要性的话题。在对照研究中,关于CJ与华法林相互作用的轶事报道大多未得到证实。30名接受稳定华法林抗凝治疗(国际标准化比值[INR]为1.7 - 3.3)的患者被随机分为两组,一组每天饮用240 mL的CJ,另一组每天饮用240 mL颜色和味道匹配的安慰剂饮料,持续2周。在这2周期间以及1周的随访期内,测量INR值以及R - 华法林和S - 华法林的血浆水平。CJ组和安慰剂组(分别为n = 14和16)的血浆R - 华法林和S - 华法林平均浓度无显著差异。8名患者(4名饮用CJ,4名饮用安慰剂)在治疗期间出现INR轻度升高(范围为3.38 - 4.52)。仅在治疗第12天,平均INR有显著差异(P <.02);在所有其他时间点,两组无差异。蔓越莓汁对血浆S - 华法林或R - 华法林水平无影响,排除了药代动力学相互作用。CJ在单个时间点对INR有虽小但具有统计学意义的药效学增强作用,这在临床上不太可能具有重要意义,可能是随机变化。轶事报道中归因于CJ的华法林抗凝增强作用可能代表一种偶然的时间关联。