Protein binding of clindamycin in sera of patients with AIDS
Protein binding of clindamycin in sera of patients with AIDS
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DOI：
10.1128/aac.40.5.1134
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发表时间：
1996-05-01
影响因子：
4.9
通讯作者：
Gambertoglio, JG
中科院分区：
文献类型：
--
作者：
Flaherty, JF;Gatti, G;Gambertoglio, JG
与健康对照组相比，艾滋病患者克林霉素的药代动力学发生了改变。为了更好地了解这些差异，我们对艾滋病患者血清中克林霉素的蛋白结合进行了研究。15名艾滋病患者和15名健康志愿者单次口服和静脉注射600 mg克林霉素，分别在高、中、低三个时间点采集血样。用超滤法测定蛋白结合力，用气相色谱法测定克林霉素的总浓度和游离浓度。艾滋病患者的α(1)-酸性糖蛋白值大约是健康志愿者的两倍(平均+/-标准差，103+/-27对61+/-11 mg/dl；P=0.001)。总体而言，艾滋病患者的血清蛋白结合水平较高(平均+/-标准差，83+/-7vs78%+/-8%；P=0.0001)，这可能是这些患者α(1)-酸性糖蛋白水平升高的结果。在研究的大多数时间点，艾滋病患者血浆中克林霉素的总浓度显著高于对照组，而在口服和静脉给药后的每个采样时间，各组间的血药浓度差异无统计学意义。蛋白结合力增加可能部分解释了克林霉素在艾滋病患者中的药代动力学变化；然而，不能排除其他因素。
Patients with AIDS have altered pharmacokinetics of clindamycin compared with those of healthy control subjects. In an attempt to better understand these differences, we undertook a study of protein binding of clindamycin in sera of patients with AIDS. Fifteen patients with AIDS and 15 healthy volunteers were given a single 600-mg dose of clindamycin orally and intravenously, and serum samples were collected at three time points corresponding to high, midpoint, and low clindamycin concentrations. Protein binding was determined by ultrafiltration, and total and unbound clindamycin concentrations were measured with a gas chromatography assay. AIDS patients had alpha(1)-acid glycoprotein values approximately twice those of healthy volunteers (mean +/- standard deviation, 103 +/- 27 versus 61 +/- 11 mg/dl; P = 0.001). Overall, serum protein binding levels were higher in AIDS patients (mean +/- standard deviation, 83 +/- 7 versus 78% +/- 8%; P = 0.0001), which is likely the result of increased alpha(1)-acid glycoprotein levels in these patients. Total concentrations of clindamycin in plasma were significantly higher in AIDS patients at most time points studied, while unbound serum clindamycin concentrations did not differ among the groups at each sampling time after both oral and intravenous dosing. Increased protein binding may partly explain the altered pharmacokinetic disposition of clindamycin in AIDS patients; however, other factors cannot be excluded.