We tested this hypothesis by measuring TPMT activity in erythrocyte preparations from adults and newborns and observed polymorphic distribution of TPMT activity in the adult and newborn erythrocytes. The activity of TPMT was higher in red cells from the newborns than adults. The frequency distribution of TPMT activity was also investigated in the liver and kidney. In the kidney, TPMT activity fell into two subgroups, whereas in the liver the distribution pattern was more complex. The activity of TPMT in erythrocytes and liver from the same subject was correlated, but the values of only half the cases fell within the 95% confidence limits, suggesting that the control of hepatic and/or erythrocyte TPMT is multifactorial.

Budesonide, a corticosteroid used in the treatment of asthma and allergic reactions, is almost entirely cleared by metabolism in man. We describe the sulphation of budesonide in human liver and lung and provide evidences that the sulphation of budesonide is catalysed by testosterone sulphotransferase. A rapid and reproducible radiometric assay for budesonide sulphotransferase is described. Liver specimens were obtained from 35 men and 65 women and lung specimens from 2 women and 17 men. The average hepatic budesonide sulphation rate was significantly higher in men (41.1 pmol.min-1.ml-1) than women (28.2 pmol.min-1.mg-1). In the lung, the mean budesonide sulphation rate was 5.0 pmol.min-1.mg-1. Testosterone strongly inhibited the hepatic sulphation of budesonide, whereas p-nitrophenol and dopamine were poor inhibitors; the IC50 was 7.0 uM (testosterone), 320 uM (p-nitrophenol) and 510 uM (dopamine). The hepatic rates of testosterone, p-nitrophenol and dopamine sulphation were measured in the same samples assayed for budesonide sulphotransferase. There was a correlation between the hepatic rates of budesonide and testosterone sulphation (P < 0.001; r = 0.810). The activity of testosterone sulphotransferase was significantly greater in men than women (22.0 vs. 17.2 pmol.min-1.mg-1), whereas those of dopamine and p-nitrophenol sulphotransferase were not sex dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

1. The methylation of captopril was studied in the microsomal fraction obtained from 87 specimens of human liver and 70 specimens of human renal cortex. 2. The rate captopril methylation ranged over one order of magnitude in the liver and kidney. In the human liver, the mean (+/- SD) rate of captopril methylation (pmol/min/mg) was significantly (p < 0.001) greater in women (199 +/- 97) than in men (126 +/- 88), whereas in the kidney no sex-difference was observed, and the mean (+/- SD) of all cases was 47 +/- 23 pmol/min/mg. 3. In the kidney, the statistical analysis revealed the presence of two subgroups in the rate of captopril methylation and their mean (+/- SD) estimates were 42.5 +/- 13.9 and 90.3 +/- 12.0 pmol/min/mg (p < 0.05). Of the population, 84% fell in the former and the remaining 16% in the latter subgroup. 4. Captopril is mainly eliminated by metabolism and its bioavailability is 65%. Methylation is one of the metabolic routes of captopril and its variability may contribute, to some extent, to modulate the intracellular concentration of this drug.