Brannan M D, Reidenberg P, Radwanski E, Shneyer L, Lin C C, Cayen M N, Affrime M B
Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Clin Pharmacol Ther. 1995 Sep;58(3):269-78. doi: 10.1016/0009-9236(95)90243-0.
To evaluate the effects of coadministration of loratadine and erythromycin on the pharmacokinetics and electrocardiographic repolarization (QTc) pharmacodynamics of loratadine and its metabolite descarboethoxyloratadine in healthy volunteers.
Twenty-four healthy volunteers were studied in a prospective, double-blind crossover design while confined in a Clinical Research Center. The primary pharmacodynamic end point of the study was the difference between baseline and day 10 mean QTc intervals obtained from surface electrocardiograms. Plasma concentrations of loratadine, descarboethoxyloratadine, and erythromycin were measured on treatment day 10 for pharmacokinetic analysis. Subjects received in random sequence the following three treatments for 10 consecutive days during three separate study periods: 10 mg loratadine every morning plus 500 mg erythromycin stearate every 8 hours, or 10 mg loratadine every morning plus placebo every 8 hours, or placebo every morning plus 500 mg erythromycin stearate.
Concomitant administration of loratadine and erythromycin was associated with increased plasma concentrations of loratadine (40% increase in area under the plasma concentration-time curve [AUC]) and descarboethoxyloratadine (46% increase in AUC) compared with loratadine alone. Analysis of variance showed no difference between the treatment groups in effect on QTc intervals compared with baseline, and no significant change from baseline was observed. No clinically relevant changes in the safety profile of loratadine were observed, and there were no reports of sedation nor syncope.
Although concomitant administration of loratadine and erythromycin was associated with increased plasma concentrations of loratadine and descarboethoxyloratadine, no clinically relevant changes in the safety profile of loratadine were observed. In this study, 10 mg loratadine administered orally for 10 consecutive days was well tolerated when coadministered with therapeutic doses of erythromycin stearate.
评估氯雷他定与红霉素联合给药对健康志愿者体内氯雷他定及其代谢产物去乙氧羰基氯雷他定的药代动力学和心电图复极化（QTc）药效学的影响。
24名健康志愿者在临床研究中心进行前瞻性、双盲交叉设计研究。研究的主要药效学终点是从体表心电图获得的基线与第10天平均QTc间期的差异。在治疗第10天测量氯雷他定、去乙氧羰基氯雷他定和红霉素的血浆浓度以进行药代动力学分析。在三个单独的研究期间，受试者在连续10天内随机接受以下三种治疗：每天早晨服用10mg氯雷他定加每8小时服用500mg硬脂酸红霉素，或每天早晨服用10mg氯雷他定加每8小时服用安慰剂，或每天早晨服用安慰剂加每8小时服用500mg硬脂酸红霉素。
与单独使用氯雷他定相比，氯雷他定与红霉素联合给药使氯雷他定的血浆浓度升高（血浆浓度 - 时间曲线下面积[AUC]增加40%）以及去乙氧羰基氯雷他定的血浆浓度升高（AUC增加46%）。方差分析显示，与基线相比，治疗组对QTc间期的影响无差异，且未观察到与基线有显著变化。未观察到氯雷他定安全性方面有临床相关变化，也无镇静或晕厥报告。
虽然氯雷他定与红霉素联合给药会使氯雷他定和去乙氧羰基氯雷他定的血浆浓度升高，但未观察到氯雷他定安全性方面有临床相关变化。在本研究中，连续10天口服10mg氯雷他定与治疗剂量的硬脂酸红霉素联合给药时耐受性良好。
