Metabolism of [4-14c]norethisterone in Women

Kamyab, Soraya; Fotherby, K.; Klopper, Arnold

doi:10.1677/joe.0.0410263

Cited by 36 publications

(7 citation statements)

References 14 publications

(21 reference statements)

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“…All the compounds tested had a 17,/-OH. This group is not oxidized when there is a 17a-ethinyl group, and the latter has been shown to be very resistant to metabolism (Fotherby, Kamyab, Littleton & Klopper, 1966;Kamyab, Fotherby & Steele, 1969;Williams, Nilsen & Blahey, 1967). Our studies emphasize the importance of 17a-ethinyl substitution but leave open the question whether 3-hydroxyl, aromatic A ring and 17f/-OH are necessary for inhibition of bile secretion.…”

Section: Discussionmentioning

confidence: 64%

The effect of oral contraceptive steroids on bile secretion and bilirubin Tm in rats

Heikel¹,

Lathe²

1970

British J Pharmacology

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Summary1. The effect of oestrogens and progestogens and their 17a-ethinyl derivatives on bile flow, maximum rate of bilirubin secretion, serum and liver bilirubin has been studied. 2. Both 17a-ethinyl substituted oestrogens and progestogens greatly reduced the basal bile flow. The parent compounds, oestradiol-17f3 and 19-nortestosterone had little or no effect. 3. A much larger dose of progestogens (40 mg/kg) than oestrogens (5 mg/kg) was needed. 4. Between 12 and 48 h were required for 17a-ethinyloestradiol to produce the effect. 5. Bilirubin maximum secretion rate (Tm) was little affected, the only significant reduction being produced by the 3-methyl ether of 17a-ethinyloestradiol (mestranol). 6. Rises in serum conjugated bilirubin following infusion of bilirubin were produced by 17a-ethinyloestradiol and mestranol but not by the progestogens.

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Section: Discussionmentioning

confidence: 64%

The effect of oral contraceptive steroids on bile secretion and bilirubin Tm in rats

Heikel¹,

Lathe²

1970

British J Pharmacology

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“…Subject M 3 received 1 pc [14C]norgestrel adsorbed on to lactose in a gelatine capsule orally. The details of the investiga¬ tions together with the methods used for the estimation of radioactivity in urine and blood have been described previously (Kamyab, Littleton & Fotherby, 1967;Kamyab, Fotherby & Klopper, 1968a). For the isolation and identification of norgestrel metabolites, urine from subject M 2 was pooled and extracted in 11. quantities.…”

Section: Methodsmentioning

confidence: 99%

“…DISCUSSION Norgestrel (18-methylnorethisterone) and lynestrenol (3-deoxynorethisterone) are both chemically related to norethisterone (17a-ethynyl-19-nortestosterone), but these three synthetic progestins show marked differences in biological activity. Since the methods used in the present study of the metabolism of norgestrel are similar to those used previously for lynestrenol (Kamyab, Fotherby & Klopper, 1968&) and nore¬ thisterone (Kamyab et al 1968a) it is possible to compare the metabolism of the three compounds. The recovery of radioactivity in urine after the injection of norgestrel (40%) was similar to that obtained with lynestrenol (43-7%) but less than that obtained with norethisterone (53-9%).…”

Section: Radioactivity In Urine and Bloodmentioning

confidence: 99%

Metabolism of [14c]norgestrel in Man

Littleton¹,

Fotherby²,

Dennis³

1968

Journal of Endocrinology

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14C]Norgestrel was administered to seven human subjects and 43 % of dose was excreted in the urine within 5 days; the biological half-life of the radioactivity was 24 hr. Enzymic hydrolysis released only 32% of the the urinary radioactivity and a further 25 % was excreted as sulphate conjugates. The metabolites excreted in the urine were much less polar than those following the administration of the related compounds, norethisterone or lynestrenol. The 3\g=a\OH,5\g=b\ and 3\g=b\OH,5\g=b\ isomers of the tetrahydronorgestrel (13\g=b\-ethyl-17\g=a\-ethynyl-5\g=b\-gonane-3\g=a\,17\g=b\-diol) were isolated from urine and identified by mass spectrometry and thin-layer and gas\p=m-\liquid chromatography. Plasma radioactivity decreased more rapidly than after the administration of norethisterone and lynestrenol. About 2% of the administered dose was converted to acidic compounds. There was no apparent difference in the rate of excretion of radioactivity or in the metabolites after either oral or intravenous administration of norgestrel.

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“…Since these investigations were carried out on the day on which the women were subjected to laparotomy, a 24 h sample of urine was collected starting at the time of injection of the dose, and blood samples were taken 1, 3 and 24 h after admini¬ stration of the dose in order to see whether there was any difference in these values from those obtained in normal subjects not subjected to an operation (Kamyab, Fotherby & Klopper, 1968). The mean values for the amount of administered dose recovered in urine and for the extraction of radioactivity from urine are compared in Table 7 with values obtained in normal subjects.…”

Section: Radioactivity In Urine and Bloodmentioning

confidence: 99%

“…These values are similar to those obtained previously in normal subjects and suggest that no major change in the metabolism of norethisterone occurred in the patients during the pre-operative period. DISCUSSION Although the metabolism of norethisterone in vivo has been investigated in man by Layne, Golab, Arai & Pincus (1963), Murata (1967), Kamyab et al (1968) and Gerhards, Hecker, Hitze, Nieuweboer & Bellmann (1971), no study of the localization of this synthetic progestogen in human tissues has been reported. The present investigation shows that norethisterone passes into adipose tissue and all the tissues of the reproductive tract within 1 h of injection, reaching particularly high con¬ centrations in endometrium and stroma.…”

Section: Radioactivity In Urine and Bloodmentioning

confidence: 99%

Localization of Norethisterone in the Reproductive Tract of Women

Reed¹,

Fotherby²,

Peck³

et al. 1973

Journal of Endocrinology

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3H]Norethisterone was administered to women 1, 3 and 24 h before hysterectomy, when samples of blood, adipose tissue and tissues from the reproductive tract were obtained. At 1 h the highest concentrations of radioactivity were found in endometrium and stroma (0\m=.\77 and 0\m=.\78% respectively of the dose per 100 g tissue), the values in other tissues varying from 0\m=.\13to 0\m=.\39 %. By 3 h there was a decrease in the concentration in all tissues except adipose tissue and plasma and at this time the range of concentrations in all tissues, apart from plasma (0\m=.\40%), were similar (0\m=.\08 to 0\m=.\19%). There was a further decrease by 24 h. Mean values for the amount of radioactivity present in the tissues at 1 h were: uterus, 0\m=.\55%; adipose tissue, 21\m=.\6%;blood, 10\m=.\1%.By 24 h these values had decreased to 0\m=.\1, 7\m=.\0and 6\m=.\6%respectively. In adipose tissue most of the radioactivity was present in the freely extractable state at all times studied, whereas in myometrium and cervix the amount of radioactivity freely extractable at 1 h (77%) had decreased by 24 h (39\m=.\0%). In plasma the amount of conjugated radioactivity increased from 54% at 1 h to 88% by 24 h. Whereas at 1 h most metabolites in plasma were conjugated as sulphates, by 24 h glucuronide conjugates were also important. In myometrial tissue 17\m=.\5to 47\m=.\8% of the radioactivity was associated with the nuclear fraction.

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Metabolism of [4-14c]norethisterone in Women

Cited by 36 publications

References 14 publications

The effect of oral contraceptive steroids on bile secretion and bilirubin Tm in rats

The effect of oral contraceptive steroids on bile secretion and bilirubin Tm in rats

Metabolism of [14c]norgestrel in Man

Localization of Norethisterone in the Reproductive Tract of Women

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