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首页> 外文会议>Collegium Internationale Allergologicum >Pharmacodynamics of Latest Generation H_1.Antihistamines: Relevance of Drug Concentrations at Receptor Sites and of Affinity Values for H_1 Receptors
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Pharmacodynamics of Latest Generation H_1.Antihistamines: Relevance of Drug Concentrations at Receptor Sites and of Affinity Values for H_1 Receptors

机译：最新一代H_1的药效学.AntiHistamines：H_1受体的受体位点和亲和力值的相关性的相关性

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Introduction: The percentage of receptor occupancy has been shown to correlate with the percentage of inhibition of histamine-induced wheal and flare by an H_1-antihistamine. The estimation of receptor occupancy requires the availability of both the drug concentration at receptor sites and affinity of the drug for the receptor. Classically, free plasma concentrations, calculated from plasma concentrations using plasma protein binding, are used as an approximation of the drug concentration at receptor sites. The purpose of this work is to estimate the drug concentration at receptor sites by an alternative approach, using the volume of distribution and the skin concentrations of the drug. Methods and Results: Skin concentrations were measured by validated methods in samples from 18 adult allergic volunteers 24 h after administration of 5 mg oral levocetirizine or desloratadine. Mean values were 40.7 and 56.3 ng/g, respectively). The volumes of distribution (V/F) of levocetirizine and desloratadine are 28 and 3430 L, respectively for a 70 kg man. Using the formula V/F =V_p + f_(uP)/f_(uT) V_(TW), where F = absolute bioavailability (assumed to be 1), Vp = volume of plasma (3.2 L for a 70 kg man), V_(TW) = volume in which the drug is distributed outside plasma, f_(uP) = fraction unbound in plasma and f_(uT) = fraction unbound in tissue, it is possible to calculate f_(uT) (0.14-0.052 for levocetirizine and 0.0017-0.0006 for desloratadine) and therefore the free tissue (skin) concentration by the relationship f_(uT) centre dot C_T, where C_T is the total tissue (skin) concentration. Based on these calculations, free skin concentrations ranged between 2.12-5.70 and 0.034-0.096 ng/g for levocetirizine and desloratadine, respectively. Conclusion: The estimated free skin concentration values are very similar to free plasma concentrations. Therefore, the free skin/plasma concentrations should be used to estimate the receptor occupancy by an Hi-antihistamine. High skin concentrations simply reflect an extensive distribution of a drug (skin approx= 19% of body volume) and not necessarily the drug concentration at receptor sites, whereas high free skin concentrations are crucial for the efficiency of a drug given for skin allergic problems.
机译：引言：已显示受体占患者的百分比与H_1-抗组胺素的组胺诱导的击打的抑制百分比相关。受体占用率的估计需要受体位点的药物浓度和药物对受体的亲和力。经典地，根据使用血浆蛋白结合从血浆浓度计算的游离血浆浓度，用作受体位点的药物浓度的近似。本作作品的目的是通过使用替代方法来估计受体位点的药物浓度，使用药物的体积和药物的皮肤浓度。方法和结果：通过从18名成人过敏志愿者的样品中的验证方法测量皮肤浓度，从而在给药5mg口服左甲左甲嗪或氯丙氨酸后24小时。平均值分别为40.7和56.3ng / g）。 Levocetirizine和DeslorataDine的分布（V / F）分别为28和3430 L，分别为70公斤男性。使用公式v / f = v_p + f_（向上）/ f_（ut）v_（tw），其中f =绝对生物利用度（假设为1），vp =等离子体的体积（3.2 l为70 kg man）， v_（tw）=其中药物分布在血浆外部的外部，f_（向上）=血浆中的馏分和f_（ut）=组织中的馏分未结合，可以计算f_（ut）（0.14-0.052用于Levocetizine和0.0017-0.0006的异氯嘌呤），因此通过关系的无自由组织（皮肤）浓度F_（UT）中心点C_T，其中C_T是总组织（皮肤）浓度。基于这些计算，分别在2.12-5.70和0.034-0.096 ng / g的游离皮肤浓度分别为左旋甲基嗪和氯乙酰胺。结论：估计的自由皮肤浓度值与游离等离子体浓度非常相似。因此，可使用自由的皮肤/血浆浓度来估计Hi-anthistamine的受体占用。高皮肤浓度仅仅反映了药物（皮肤约= 19％的体积）的广泛分布，并且不一定是受体位点的药物浓度，而高自由皮肤浓度对于皮肤过敏问题给药的药物的效率至关重要。

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