International Pharmaceutical Research Center, Amman, Jordan.
Clin Ther. 2010 Feb;32(2):391-5. doi: 10.1016/j.clinthera.2010.02.001.
Loratadine is a long-acting tricyclic antihistamine with selective peripheral histamine H(1)-receptor antagonist activity. Loratadine 10-mg tablets have been reported to be rapidly absorbed after once-daily administration for 10 days in healthy adult subjects, with a T(max) of 1.3 hours for loratadine and 2.5 hours for its major active metabolite, descarboethoxyloratadine. The t(1/2) in normal adult subjects has been reported to be 8.4 hours (range, 3-20 hours) for loratadine and 28 hours for its metabolite.
The aim of this study was to determine the population pharmacokinetics of loratadine after oral administration.
A retrospective analysis was conducted of prior noncompartmental analysis results from healthy white Jordanian male subjects who participated in 2 pharmacokinetic studies. After a 10-hour overnight fast, a single 10-mg loratadine tablet was administered orally followed by 240 mL of water. Blood samples were collected before dosing and at 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours after dosing. Mean and population plasma level profiles were examined. The calculated primary and secondary pharmacokinetic parameters were V(d)/F, k(e), absorption rate constant, lag time, distribution rate constant, redistribution rate constant, T(max), and C(max).
A total of 72 healthy male subjects with a mean (SD) age of 23 (3.57) years participated in the 2 studies. The analytical method was linear over the concentration range from 0.10 to 20.00 ng/mL (r > 0.999). The lower limit of quantitation was 0.1 ng/mL with 95% accuracy. Precision, expressed as %CV, was 7.44%. Intraday accuracy ranged from 91.9% to 97.2% at high and low quality control levels, respectively. Interday accuracy ranged from 93.57% (%CV, 4.35%) to 98.78% (%CV, 5.78%), respectively. Population ke, t(1/2), absorption rate constant, and absorption t(1/2) were 0.19 hour(-1), 3.65 hours, 1.31 hours(-1), and 0.53 hour, respectively. Distribution rate constant, redistribution rate constant, and lag time were 0.31 hour(-1), 0.02 hour(-1), and 0.32 hour, respectively. The noncompartmental estimate for C(max) was 3.02 ng/mL, which occurred at 1.30 hours, with a t(1/2) of 5 hours and a k(e) of 0.14 hour(-1). No adverse events were recorded during the study.
The population t(1/2) for loratadine was 3.65 hours in this group of healthy white Jordanian male volunteers, shorter than that observed in previous research.
氯雷他定是一种长效三环类抗组胺药，具有选择性外周组胺 H（1）-受体拮抗剂活性。在健康成年受试者中，每日一次服用 10 毫克片剂 10 天后，氯雷他定的 T（max）为 1.3 小时，其主要活性代谢物去羧乙基氯雷他定为 2.5 小时。正常成年受试者的 t（1/2）为氯雷他定为 8.4 小时（范围 3-20 小时），其代谢物为 28 小时。
本研究旨在确定口服氯雷他定后的群体药代动力学。
对参加了 2 项药代动力学研究的健康的约旦白人男性志愿者的先前非房室分析结果进行了回顾性分析。禁食 10 小时后，口服单剂量 10 毫克氯雷他定片，然后饮用 240 毫升水。在给药前和给药后 0.33、0.66、1、1.5、2、3、4、6、8、10、12、16、24、36、48、72 和 96 小时采集血样。检查平均和群体血浆水平曲线。计算的主要和次要药代动力学参数为 V（d）/F、k（e）、吸收速率常数、滞后时间、分布速率常数、再分布速率常数、T（max）和 C（max）。
共有 72 名平均（标准差）年龄为 23（3.57）岁的健康男性志愿者参加了这两项研究。分析方法的线性范围为 0.10 至 20.00ng/ml（r>0.999）。定量下限为 0.1ng/ml，准确度为 95%。精密度（%CV）为 7.44%。在高、低质控水平下，日内准确度分别为 91.9%至 97.2%。日间准确度分别为 93.57%（%CV，4.35%）至 98.78%（%CV，5.78%）。群体 ke、t（1/2）、吸收速率常数和吸收 t（1/2）分别为 0.19 小时（-1）、3.65 小时、1.31 小时（-1）和 0.53 小时。分布速率常数、再分布速率常数和滞后时间分别为 0.31 小时（-1）、0.02 小时（-1）和 0.32 小时。非房室估算的 C（max）为 3.02ng/ml，发生在 1.30 小时，t（1/2）为 5 小时，k（e）为 0.14 小时（-1）。研究过程中未记录到不良事件。
在这群健康的约旦白人男性志愿者中，氯雷他定的群体 t（1/2）为 3.65 小时，短于以往研究观察到的时间。
