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[三种8-甲氧基补骨脂素制剂的药代动力学比较及临床情况]

[Pharmacokinetic comparison of 3 8-methoxypsoralen preparations and clinical aspects].

作者信息

Walther T, Haustein U F, Quednow B, Meyer F P

机构信息

Klinik für Hautkrankheiten, Bereiches Medizin, Karl-Marx-Universität Leipzig.

出版信息

Hautarzt. 1990 Jun;41(6):317-21.

PMID:2380068
Abstract

In order to register the inter- and intraindividual variability of serum levels of 8-methoxypsoralen (MOP) (Oxsoralen, n = 12; Geroxalen, n = 46; Mopsoralen, n = 30), we investigated a total of 1,276 serum samples obtained at 11 patient appointments over 8 h in 88 patients and compared the individual serum concentrations - time curves with the pharmacokinetic parameters Cmax (maximal serum concentration) on the time tmax, as well as the AUC value (area under the curve) as a parameter of bioavailability. The individual serum concentration value showed a high interindividual variability (Oxsoralen Cmax: 47-473 ng.ml-1; Geroxalen Cmax: 37-416 ng.ml-1 and Mopsoralen Cmax: 44-300 ng.ml-1) and preparation specific differences (Oxsoralen Cmax: 188 +/- 125 ng.ml-1; tmax: 2.0 +/- 0.6 h; AUC: 461 +/- 322 ng.ml-1.h; Geroxalen Cmax: 193 +/- 87 ng.ml-1; tmax: 0.9 +/- 0.4 h; AUC: 290 +/- 198 ng.ml-1.h; Mopsoralen Cmax: 164 +/- 71 ng.ml-1; tmax: 1.7 +/- 0.5 h; AUC: 389 +/- 221 ng.ml-1.h). On repeated administration of Geroxalen (n = 16) and Mopsoralen (n = 12), minimal intraindividual distributions were noted, so the mean serum concentration curves did not show a significant difference. The importance of 8-MOP serum level determinations for better puva therapy, particularly in therapeutic failure in problem cases, is discussed.

摘要

为记录8-甲氧基补骨脂素(MOP)(甲氧沙林,n = 12;杰罗沙林,n = 46;补骨脂素,n = 30)血清水平的个体间和个体内变异性,我们对88例患者在8小时内的11次患者预约就诊时采集的总共1276份血清样本进行了研究,并将个体血清浓度-时间曲线与药代动力学参数tmax时的Cmax(最大血清浓度)以及作为生物利用度参数的AUC值(曲线下面积)进行了比较。个体血清浓度值显示出较高的个体间变异性(甲氧沙林Cmax:47 - 473 ng/ml;杰罗沙林Cmax:37 - 416 ng/ml;补骨脂素Cmax:44 - 300 ng/ml)以及制剂特异性差异(甲氧沙林Cmax:188±125 ng/ml;tmax:2.0±0.6小时;AUC:461±322 ng/ml·h;杰罗沙林Cmax:193±87 ng/ml;tmax:0.9±0.4小时;AUC:290±198 ng/ml·h;补骨脂素Cmax:164±71 ng/ml;tmax:1.7±0.5小时;AUC:389±221 ng/ml·h)。在重复给予杰罗沙林(n = 16)和补骨脂素(n = 12)时,观察到最小的个体内分布差异,因此平均血清浓度曲线未显示出显著差异。本文讨论了8 - MOP血清水平测定对于优化光化学疗法(PUVA)的重要性,特别是在疑难病例治疗失败的情况下。

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