血药浓度监测中内源性地高辛样免疫活性物质的临床意义

 目的直接测定和间接估算心功能不全患者的血清内源性地高辛样免疫活性物质(digoxin-like immunoreactive substances,DLIS)的浓度。方法用荧光偏振免疫分析法(FPIA，TDx仪)测定15例未接受地高辛治疗的心衰患者血清表观地高辛(DLIS)浓度。对12例已用地高辛的心衰患者，在测定地高辛总浓度(FPIA)和游离浓度(超滤/FPIA)后，计算其血清DLIS浓度。结果以TDx仪最低检测限0.26 nmol·L^-1为检出标准，心衰患者血清DLIS检出阳性率为46.7%(7/15)，其浓度范围(0.26～1.52) nmol·L^-1，平均浓度(0.55±0.44) nmol·L^-1；其中1例患者血清DLIS浓度高达1.52 nmol·L^-1。已用地高辛的心衰患者血清实测地高辛游离浓度为(0.79±0.48)(0.41～2.10) nmol·L^-1；实测地高辛总浓度为(1.31±0.80) nmol·L^-1，明显高于计算的地高辛总浓度(1.05±0.64) nmol·L^-1(P＜0.01)。计算的DLIS浓度为(0.26±0.19)(0.07～0.76) nmol·L^-1。结论心功能不全患者血清中含有一定量的DLIS；提示这些患者使用地高辛治疗时，免疫分析法测得的血清地高辛浓度结果易引起“过高估计”。

Clinical significance of digoxin-like immunoreactive substances in sera in the therapeutic drug monitoring

OBJECTIVE To determine directly and calculate indirectly the concentrations of digoxin like immunoreactive substances(DLIS)in serum in the patients with cardiac insufficiency. METHODS The apparent digoxin concentrations in serum were determined in 15 inpatients with cardiac insufficiency without receiving digoxin by fluorescence polarization immunoassay(FPIA) with TDx analyser.The concentrations of serum DLIS in twelve patients with cardiac failure were calculated after determinations of total digoxin by FPIA and free digoxin by ultrafiltration with FPIA.The lowest measureble level for FPIA with TDx analyser was 0.26 nmol·L^-1. RESULTS In the patients with cardiac insufficiency not receiving digoxin,the positive ratio for determination of DLIS was 46.7%(7 in 15 cases),and its mean serum concentration was (0.55±0.44) nmol·L^-1(range 0.26～1.52 nmol·L^-1).In the patients with cardiac failure receiving digoxin therapy,the free digoxin concentration in serum determined was (0.79±0.48)(0.41～2.10) nmol·L^-1.The total digoxin concentration determined(1.31±0.80 nmol·L^-1) was significantly higher than the calculated total digoxin(1.05±0.64 nmol·L^-1)(P＜0.01).The calculated DLIS concentration was (0.26±0.19)(0.07～0.76) nmol·L^-1.The results suggested the presence of elevated DLIS in serum for these patients above and were well consistent with that obtained by recently published method of Dasgupta et al. CONCLUSION There are certain increased concentrations of DLIS in sera of the patients with cardiac insufficiency,suggesting that digoxin levels measured by immunoassay method must be interpreted carefully in these patients after treatment with digoxin or other digitalis preparations.