Pawlotsky Y, Le Dantec P, Jacquelinet C, Lapicque F, Goasguen J, Perdriger A, Veillard E, Guggenbuhl P, Netter P
Rheumatology Department, Rennes Teaching Hospital, France.
Rev Rhum Engl Ed. 1996 Mar;63(3):179-87.
The goal of this study was to look for correlations between the severity of chronic inflammatory joint disease and pharmacokinetic parameters of nonsteroidal antiinflammatory drugs. Disease severity data (pain severity and magnitude of abnormalities in laboratory tests for inflammation) and pharmacokinetic data (area under the curve in the morning (AUCm) and maximum plasma concentration (Cmax) were collected during a prospective, randomized, double-blind, parallel-group study. Two groups of nine and 11 patients, respectively, were given 300 mg etodolac b.i.d or 50 mg indomethacin b.i.d. by the oral route, for three days, after a 36-hour placebo washout. Univariate analyses demonstrated statistically significant negative correlations between pharmacokinetic parameters of both study drugs and a number of disease severity parameters. In the multivariate analysis of data for etodolac, the sigma erythrocyte sedimentation rate contributed significantly to variations in all pharmacokinetic parameters and explained 100% of the variations in free S-enantiomer AUCm and in total and free S-enantiomer Cmax. For indomethacin, pain contributed to variations in Cmax values of the total and free forms; the sigma erythrocyte sedimentation rate was also a factor in variations in total indomethacin. These negative correlations suggest that severity of chronic inflammatory joint disease may influence the pharmacokinetics of nonsteroidal antiinflammatory drugs.
本研究的目的是寻找慢性炎症性关节疾病的严重程度与非甾体抗炎药药代动力学参数之间的相关性。在前瞻性、随机、双盲、平行组研究中收集疾病严重程度数据（疼痛严重程度和炎症实验室检查异常程度）和药代动力学数据（早晨曲线下面积（AUCm）和最大血浆浓度（Cmax））。在经过36小时的安慰剂洗脱期后，两组分别为9名和11名患者，通过口服途径给予300mg依托度酸每日两次或50mg吲哚美辛每日两次，持续三天。单因素分析表明，两种研究药物的药代动力学参数与一些疾病严重程度参数之间存在统计学上显著的负相关。在依托度酸数据的多因素分析中，红细胞沉降率对所有药代动力学参数的变化有显著贡献，并解释了游离S-对映体AUCm以及总S-对映体和游离S-对映体Cmax变化的100%。对于吲哚美辛，疼痛导致总形式和游离形式的Cmax值发生变化；红细胞沉降率也是总吲哚美辛变化的一个因素。这些负相关表明，慢性炎症性关节疾病的严重程度可能会影响非甾体抗炎药的药代动力学。
