METABOLISM OF PREDNISOLONE BY THE ISOLATED PERFUSED HUMAN PLACENTAL LOBULE

被引:17
作者
ADDISON, RS
MAGUIRE, DJ
MORTIMER, RH
CANNELL, GR
机构
[1] ROYAL BRISBANE HOSP,CONJOINT INTERNAL MED LAB,HERSTON RD,BRISBANE,QLD 4029,AUSTRALIA
[2] GRIFFITH UNIV,DIV SCI & TECHNOL,NATHAN,QLD 4111,AUSTRALIA
基金
英国医学研究理事会;
关键词
D O I
10.1016/0960-0760(91)90016-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previous studies of the metabolism of 11-beta-hydroxy corticosteroids by placental tissue have indicated that the only product is the C11-oxidized metabolite. In the present study we have re-examined the metabolism of prednisolone in the isolated, perfused, dual recirculating human placental lobule, using a perfusate based on tissue culture medium 199. Four metabolites were identified in both the maternal and fetal compartments in 6 h perfusions by comparison of relative retention times measured by HPLC and capillary gas chromatography (GC) and of mass spectra recorded by capillary gas chromatography-mass spectrometry (GC-MS) with those of authentic reference standards. The steroids were derivatized as the MO-TMS ethers for mass spectral measurements. Analysis of samples from five perfusion experiments resulted in the following percentage conversions after 6 h perfusion (mean +/- SD, maternal and fetal perfusate, respectively): prednisone (49.1 +/- 7.8, 49.1 +/- 6.6), 20-alpha-dihydroprednisone (0.84 +/- 0.29, 0.81 +/- 0.35), 20-beta-dihydroprednisone (39.1 +/- 6.7, 39.2 +/- 5.9), 20-beta-dihydroprednisolone (6.8 +/- 2.7, 6.3 +/- 1.6) and unmetabolized prednisolone (4.1 +/- 1.8, 4.6 +/- 2.1). No evidence was found for metabolites formed by 6-beta-hydroxylation or cleavage of the C-17-C20 bond.
引用
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页码:83 / 90
页数:8
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