The biliary and urinary metabolites of [3H]17α-ethynylestradiol in women

Abstract

The metabolism of 17 alpha-ethynyl[6,7-3H]estradiol (3H-EE2) (50 micrograms) given orally was studied in two groups of women: (a) six subjects from whom duodenal bile samples were obtained after 4 h by endoscopic aspiration; (b) two subjects with bile-duct (T-tube) drainage. The first group eliminated 16.6 +/- 7.8% (mean +/- S.D.) of the dose in urine over 72 h, the second group 28.6% and 27.5%. Biliary excretion by the latter was 41.9% and 28.3% of the dose, respectively, during the first 24 h after dosing. The metabolites excreted in bile and urine were largely polar conjugates: 1-12% of the 3H was ether extractable. Approx. 70-90% of urinary and biliary 3H was extractable following beta-glucuronidase-arylsulphohydrolase hydrolysis. Both beta-glucuronides and arylsulphates were excreted. Unchanged 3H-EE2 was the principal 3H-labelled component of the glucuronide and arylsulphate fractions of bile, and it was a major component of urinary fractions. 2-Hydroxy-EE2 and 2-methoxy-EE2 were identified as conjugated biliary metabolites.

A comparative study of the formation of chemically reactive drug metabolites by human liver microsomes.

“…Amodiaquine, ethinyloestradiol, mianserin and phenytoin were appreciably metabolized to stable metabolites (Table 6), most of which were identified as known metabolites (Claesen et al, 1982;De Jongh et al, 1981;Maggs et al, 1983b;Winstanley et al, 1987) There is increasing acceptance of a causal relationship between the toxicity associated with certain drugs and other chemicals and their ability to form chemically reactive metabolites that can bind covalently to endogenous macromolecules. Generally, as in the case of paracetamol (Jollow et al, 1973) and phencyclidine (Law, 1981) a cytotoxic effect is postulated, with the metabolite combining with functionally important protein groups such as thiols on enzymes (Jewell et al, 1982).…”

Occurrence and fate of steroid estrogens in the largest wastewater treatment plant in Beijing, China

“…Previous research has shown E3 is excreted mainly by pregnant women (D'Ascenzo et al 2003). In addition, EE2 is the main ingredient of the contraceptive pill, with an average daily dose of 35 μg taken for 21 of a 28-day cycle (Ranney 1977;Maggs et al 1983;Katzung 1995). The higher influent concentration of estrogens in the present study may be due to a higher population density and birthrate in Beijing.…”

Evaluation of Committee on Safety of Medicines yellow card reports on oral contraceptive‐drug interactions with anticonvulsants and antibiotics.

“…Individuals at risk are most probably (but not exclusively) women with a low bioavailability of EE due to extensive steroid metabolism in the gut wall and liver; a large enterohepatic circulation of EE and a particularly susceptible gut microflora able to hydrolyse steroid conjugates (Back & Orme, 1984;Shenfield, 1986). It is worth speculating that from a metabolic point of view, a woman who was a 'poor' hydroxylator of EE would probably form EE conjugates to a greater extent than an 'extensive' hydroxylator and hence have a potentially large enterohepatic circulation (Maggs et al, 1983) …”