Tan Keith, Brayshaw Nigel, Tomaszewski Konrad, Troke Peter, Wood Nolan
Clinical R&D, IPC 096, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent, CT13 9NJ, United Kingdom.
J Clin Pharmacol. 2006 Feb;46(2):235-43. doi: 10.1177/0091270005283837.
This study investigated the relationship between plasma voriconazole concentrations (pVC) and risk of visual adverse events (VAEs) or liver function test (LFT) abnormalities using longitudinal logistic regression. Seven-day mean pVC were calculated from 2,925 plasma samples (1,053 patients); in each 7-day period, the presence or absence of VAEs/abnormal LFTs was analyzed as a binary outcome variable. There was a relationship between pVC and risk of VAE (P = .011) and a weaker, but statistically significant, association with risk of aspartate transaminase (AST), alkaline phosphatase (ALP), or bilirubin but not alanine transaminase (ALT) abnormalities. The odds ratios of LFT abnormalities per 1 mug/mL pVC increase ranged from 1.07 to 1.17. Maximum weekly occurrences were 10%, 8%, 5%, and 14% for AST, ALT, ALP, and bilirubin abnormalities, respectively. Receiver-operating characteristic curve analysis indicates that individual pVC cannot be used to predict subsequent LFT abnormalities.
本研究采用纵向逻辑回归分析，探讨血浆伏立康唑浓度（pVC）与视觉不良事件（VAE）风险或肝功能检查（LFT）异常之间的关系。从2925份血浆样本（1053例患者）中计算出7天的平均pVC；在每个7天周期内，将VAE/LFT异常的存在与否作为二元结果变量进行分析。pVC与VAE风险之间存在关联（P = 0.011），与天冬氨酸转氨酶（AST）、碱性磷酸酶（ALP）或胆红素异常风险之间存在较弱但具有统计学意义的关联，而与丙氨酸转氨酶（ALT）异常无关联。每增加1微克/毫升pVC，LFT异常的比值比范围为1.07至1.17。AST、ALT、ALP和胆红素异常的每周最高发生率分别为10%、8%、5%和14%。受试者工作特征曲线分析表明，个体pVC不能用于预测随后的LFT异常。
