Baltes E, Coupez R, Giezek H, Voss G, Meyerhoff C, Strolin Benedetti M
UCB Pharma, Chemin du Foriest, 1420 Braine l'Alleud, Belgium.
Fundam Clin Pharmacol. 2001 Aug;15(4):269-77. doi: 10.1046/j.1472-8206.2001.00035.x.
The primary objective of the present study was to compare the absorption and disposition of levocetirizine, the eutomer of cetirizine, when administered alone (10 mg) or in presence of the distomer. An additional objective was also to investigate the configurational stability of levocetirizine in vivo in humans. The study was performed in a randomized, two-way cross-over, single-dose design with a wash-out phase of 7 days between the two periods. A total of 12 healthy male and 12 healthy female volunteers were included in the study. Bioequivalence can be concluded from the analysis of the pharmacokinetic parameters of levocetirizine when administered alone or as the racemate cetirizine. No chiral inversion occurs in humans when levocetirizine is administered, i.e. there is no formation of the distomer. When comparing the pharmacokinetic characteristics of levocetirizine and the distomer, the apparent volume of distribution of the eutomer is significantly smaller than that of the distomer (0.41 and 0.60 L/kg, respectively). For an H1-antagonist a small distribution volume can be considered as a positive aspect, both in terms of efficacy and safety. Moreover the non-renal clearance of levocetirizine is also significantly lower than that of the distomer (9.70 and 28.70 mL/min, respectively), which constitutes an additional positive aspect particularly as far as metabolism-based drug interactions are concerned. The information collected in the present study on the pharmacokinetics of levocetirizine and the distomer provide additional reasons for eliminating the distomer and developing levocetirizine as an improvement on cetirizine.
本研究的主要目的是比较西替利嗪的优映体左西替利嗪单独给药（10毫克）或在存在其对映体的情况下的吸收和处置情况。另一个目的是研究左西替利嗪在人体内的构型稳定性。该研究采用随机、双向交叉、单剂量设计，两个周期之间有7天的洗脱期。共有12名健康男性和12名健康女性志愿者纳入该研究。通过分析左西替利嗪单独给药或作为消旋体西替利嗪给药时的药代动力学参数，可以得出生物等效性结论。左西替利嗪给药时在人体内不会发生手性转化，即不会形成对映体。比较左西替利嗪和对映体的药代动力学特征时，优映体的表观分布容积明显小于对映体（分别为0.41和0.60升/千克）。对于H1拮抗剂而言，无论是从疗效还是安全性方面考虑，较小的分布容积都可被视为一个积极因素。此外，左西替利嗪的非肾清除率也明显低于对映体（分别为9.70和28.70毫升/分钟），这尤其在基于代谢的药物相互作用方面构成了另一个积极因素。本研究收集的关于左西替利嗪和对映体药代动力学的信息为去除对映体并开发左西替利嗪以改进西替利嗪提供了更多理由。
