Identification and measurement by gas chromatography-mass spectrometry of norethindrone and metabolites in human urine and blood

Braselton, W. Emmett; Lin, T.J.; Mills, Thomas M.; Ellegood, James O.; Mahesh, Virendra B.

doi:10.1016/0022-4731(77)90210-2

Cited by 49 publications

(9 citation statements)

References 12 publications

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“…Major pathways of metabolism of synthetic gestagens are reductive and include ring A of the steroid (4). Hydroxylated metabolites usually occur to a lesser extent.…”

Section: Introductionmentioning

confidence: 99%

Interactions between clinically used drugs and oral contraceptives.

Bolt

1994

Environ Health Perspect

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Metabolism of contraceptive compounds may be influenced by various drugs. Of clinical importance is induction by barbiturates, by diphenylhydantoin, and especially by rifampicin, of enzymes that are responsible for degradation of estrogens. The major target is the hepatic microsomal estrogen-2-hydroxylase (cytochrome P450 3A4). Another type of interaction of drugs with disposition and effectiveness of estrogens is impairment of their enterohepatic circulation. This may be due to absorption of biliary estrogen conjugates (e.g., by cholestyramine) or to insufficient cleavage of the conjugate by intestinal bacteria, the latter being observed after administration of antibiotics (e.g., ampicillin, neomycin). -Environ Health Perspect 102(Suppl 9): 35-38 (1994)

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“…Major pathways of metabolism of synthetic gestagens are reductive and include ring A of the steroid (4). Hydroxylated metabolites usually occur to a lesser extent.…”

Section: Introductionmentioning

confidence: 99%

Interactions between clinically used drugs and oral contraceptives.

Bolt

1994

Environ Health Perspect

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“…About 20 years ago, Okada et al (1964) and Kamyab et al (1968) reported that about 1% of the total dose appeared as EE2 in the phenolic fraction of urine after the administration of ENT. EE2 is detected and isolated in the conjugated fraction but not in the free fraction of the urine (Braselton et al, 1977). EE2 thus isolated appears not to be easily metabolized in the body (Reed et al, 1972).…”

Section: Endocrinolmentioning

confidence: 87%

Aromatization of norethindrone to ethynylestradiol in human adult liver.

et al. 1986

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“…Norethisterone acetate-induced receptor translocation in vivo could be due to a metabolite of the progestogen, which interacted with the oestrogen receptor. Ethynyloestradiol has been identified as a metabolite of norethisterone in the rat and human (Braselton et al, 1977) although this conversion may be limited in humans (Breuer, 1970;Fotherby, 1974). However, the marked differences in the responses of the oestrogen receptors to ethynyloestradiol and norethisterone acetate injections suggest that the ligand involved in this progestogen-induced translocation is not ethynyloestradiol itself but possibly another metabolite.…”

Section: Discussionmentioning

confidence: 99%

The effects of oestrogens and progesterone on oestrogen receptors in female rat liver

Marr¹,

Elder²,

Lim³

1980

Biochemical Journal

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The administration of oestradiol-17 beta or ethynyloestradiol as well as the synthetic progestogen norethisterone acetate resulted in translocation of the oestrogen receptor. Progesterone and the synthetic progestogen (+)-norgestrel were ineffective. The increases in nuclear oestrogen receptor content 1 h after injection of each steroid were similar but different subsequently. The increase with oestradiol-17 beta extended for 3--6 h and for at least 9 h with ethynyloestradiol. With norethisterone acetate, nuclear content was still increased after 24 h. Oestrogen injection resulted in cytosol receptor depletion and a 'deficit' in receptor content extending for 6 h, whereas norethisterone acetate-induced translocation was quantitative. With injections of norethisterone acetate + ethynyloestradiol the increase at 1 h and retention of the nuclear receptors were similar to that with norethisterone acetate alone. In contrast, the depletion of cytosol receptor and its restoration were similar to that seen with ethynyloestradiol alone, suggesting that norethisterone acetate did not interfere with the oestrogen receptor replenishment. Specific binding in vitro of [3H]oestradiol-17 beta in liver cytosols was inhibited by (+)-norgestrel and norethisterone acetate, but not progesterone, at concentrations of 10--100 microM. Nuclear receptors present after norethisterone acetate injection bound oestrogen with high affinity (Kd = 1.52 nM), similar to receptors of oestrogen-injected animals. In the uterus, differential retention of nuclear receptors in response to oestrogens is associated with different cellular responses. The differences in the response of the receptor system in liver to the various steroids suggests that the corresponding tissue responses may also be dissimilar. These results are discussed in relation to the problems of liver dysfunction in oral-contraceptive users.

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Identification and measurement by gas chromatography-mass spectrometry of norethindrone and metabolites in human urine and blood

Cited by 49 publications

References 12 publications

Interactions between clinically used drugs and oral contraceptives.

Interactions between clinically used drugs and oral contraceptives.

Aromatization of norethindrone to ethynylestradiol in human adult liver.

The effects of oestrogens and progesterone on oestrogen receptors in female rat liver

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