Pacifici G M, Bigotti R, Marchi G, Giuliani L
Department of Biomedicine, Medical School, University of Pisa, Italy.
Eur J Clin Pharmacol. 1993;45(4):337-41. doi: 10.1007/BF00265951.
Minoxidil requires to be sulphated to exert its hypotensive effect. We report on interindividual variability in the rate of minoxidil sulphation in 118 specimens of human liver and in platelets obtained from 100 healthy subjects and 100 newborns. The frequency distribution histogram of the hepatic activity of minoxidil sulphotransferase was positively skewed; the mean was 631 pmol.min-1 x mg-1. After logarithmic transformation of the enzyme activity, the frequency distribution histogram became symmetrical and did not significantly deviate from normality. The rate of minoxidil sulphation was not different in platelets from adults (0.74 pmol.min-1 x mg-1) and newborns (1.16 pmol.min-1 x mg-1). The frequency distribution histograms were positively skewed and the results of normal equivalent deviation analysis was compatible with the presence of at least two subgroups of sulphotransferase in liver and platelets. Thus, two phenotypes of sulphotransferase exist in human liver and platelets, and the "extensive sulphator" phenotype contributes to skewing the frequency distribution. In platelets, the percentage of subjects that fall in the two subgroups is different at birth and in adulthood. This can explain the different shape of the frequency distribution in newborn and adult platelets and suggests that platelet minoxidil sulphotransferase undergoes modification after birth.
米诺地尔需要硫酸化才能发挥其降压作用。我们报告了118份人肝脏标本以及从100名健康受试者和100名新生儿获取的血小板中米诺地尔硫酸化速率的个体间差异。米诺地尔磺基转移酶肝脏活性的频率分布直方图呈正偏态;平均值为631 pmol·min⁻¹·mg⁻¹。对酶活性进行对数转换后,频率分布直方图变得对称,且与正态分布无显著偏差。成人血小板(0.74 pmol·min⁻¹·mg⁻¹)和新生儿血小板(1.16 pmol·min⁻¹·mg⁻¹)中米诺地尔的硫酸化速率无差异。频率分布直方图呈正偏态,正态等效偏差分析结果表明肝脏和血小板中至少存在两个磺基转移酶亚组。因此,人肝脏和血小板中存在两种磺基转移酶表型,“广泛硫酸化者”表型导致频率分布出现偏态。在血小板中,两个亚组中的受试者百分比在出生时和成年期有所不同。这可以解释新生儿和成人血小板频率分布形状的差异,并表明血小板米诺地尔磺基转移酶在出生后会发生改变。