REVERSIBLE BINDING OF 5-METHOXYPSORALEN AND 8-METHOXYPSORALEN TO HUMAN-SERUM PROTEINS (ALBUMIN) AND TO EPIDERMIS INVITRO

被引:46
作者
ARTUC, M [1 ]
STUETTGEN, G [1 ]
SCHALLA, W [1 ]
SCHAEFER, H [1 ]
GAZITH, J [1 ]
机构
[1] FREE UNIV BERLIN,RUDOLF VIRCHOW HOSP,DEPT DERMATOL,D-1000 BERLIN 65,FED REP GER
关键词
D O I
10.1111/j.1365-2133.1979.tb05645.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Binding of the two photosensitizers, 8‐methoxypsoralen (8‐MOP) and 5‐methoxypsoralen (5‐MOP), to serum proteins and to epidermis was measured. 8‐MOP binds to serum proteins with an apparent dissociation constant (Kd) of 4 × 10‐5m. Under conditions of oral therapy, serum concentrations of the photosensitizer 2 h after administration are usually in the range of 100–1000 ng per ml serum. In this concentration range, 75–80% of the drug was found to be reversibly bound to serum proteins. 5‐MOP shows a higher binding affinity to serum proteins and 98–99% of the drug is protein bound. The binding of both psoralen derivatives appears to take place mainly to serum albumin. 5‐MOP and 8‐MOP bind to different and non‐interacting sites on serum proteins and the binding of the on has no effect on the binding of the other methoxypsoralen. Both photosensitizers bind reversibly to human epidermis. 8‐MOP concentration in the epidermis is increased by ten to twenty fold compared with the equilibrium buffer. 5‐MOP shows a higher binding affinity, resulting in a higher tissue concentration of the photosensitizer. As in serum, the two drugs appear to be bound in the epidermis to independent and non‐interacting sites. No binding competition was found between the two methoxypsoralens and hydrocortisone, fluo‐cinonide and acetyl salicylic acid, either in serum or in epidermis, using up to 1000 fold higher concentrations as compared with those of 5‐MOP and 8‐MOP. Copyright © 1979, Wiley Blackwell. All rights reserved
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页码:669 / 677
页数:9
相关论文
共 12 条
  • [1] COLOWICK SP, 1969, J BIOL CHEM, V244, P774
  • [2] DETERMINATION OF 8-METHOXYPSORALEN IN PLASMA BY ELECTRON-CAPTURE GAS-CHROMATOGRAPHY
    EHRSSON, H
    EKSBORG, S
    WALLIN, I
    KALLBERG, N
    SWANBECK, G
    [J]. JOURNAL OF CHROMATOGRAPHY, 1977, 140 (02): : 157 - 164
  • [3] 8-METHOXYPSORALEN - ITS ISOLATION AND GAS-CHROMATOGRAPHIC DETERMINATION FROM AQUEOUS-SOLUTIONS AND SERUM
    GAZITH, J
    SCHAEFER, H
    [J]. BIOCHEMICAL MEDICINE, 1977, 18 (01): : 102 - 109
  • [4] 8-METHOXYPSORALEN GAS CHROMATOGRAPHIC DETERMINATION AND SERUM KINETICS
    GAZITH, J
    SCHALLA, W
    SCHAEFER, H
    [J]. ARCHIVES OF DERMATOLOGICAL RESEARCH, 1978, 263 (02) : 215 - 222
  • [5] 5-METHOXYPSORALEN (BERGAPTEN) IN PHOTOCHEMOTHERAPY OF PSORIASIS
    HONIGSMANN, H
    JASCHKE, E
    GSCHNAIT, F
    BRENNER, W
    FRITSCH, P
    WOLFF, K
    [J]. BRITISH JOURNAL OF DERMATOLOGY, 1979, 101 (04) : 369 - 378
  • [6] PHOTOSENSITIZATION OF SKIN IN VIVO BY FUROCOUMARINS (PSORALENS)
    PATHAK, MA
    KRAMER, DM
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1969, 195 (01) : 197 - &
  • [7] Rodbard D, 1975, Methods Enzymol, V36, P3
  • [8] THE ATTRACTIONS OF PROTEINS FOR SMALL MOLECULES AND IONS
    SCATCHARD, G
    [J]. ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1949, 51 (04) : 660 - 672
  • [9] RAPID, SENSITIVE GAS-CHROMATOGRAPHIC ANALYSIS OF 8-METHOXYPSORALEN IN HUMAN-PLASMA
    SCHMID, J
    KOSS, FW
    [J]. JOURNAL OF CHROMATOGRAPHY, 1978, 146 (03): : 498 - 502
  • [10] SERUM LEVEL PROFILES OF 8-METHOXYPSORALEN AFTER ORAL-ADMINISTRATION
    STEINER, I
    PREY, T
    GSCHNAIT, F
    WASHUTTL, J
    GREITER, F
    [J]. ARCHIVES OF DERMATOLOGICAL RESEARCH, 1977, 259 (03) : 299 - 301