Plasma Levels of Norethindrone After Single Oral Dose Administration of Norethindrone and Lynestrenol

Odlind, Viveca; Weiner, Erik; Victor, Arne; Johansson, Elof D. B.

doi:10.1111/j.1365-2265.1979.tb03030.x

Cited by 33 publications

(13 citation statements)

References 17 publications

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“…The mean plasma half-life of NET in the healthy volunteers was around 11 h. The half-life of NET after a single oral dose has previously been calcu¬ lated to around 8 h (Odlind et al 1979). The difference found could be due to the high level of SHBG found at the end of the treatment cycle.…”

Section: Discussionmentioning

confidence: 95%

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Free norethisterone as reflected by saliva concentrations of norethisterone during oral contraceptive use

Odlind

Johansson

1981

Acta Endocrinologica

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Saliva and plasma concentrations of norethisterone (NET) were determined by a radioimmunoassay in 5 healthy women and in one epileptic woman on phenytoin treatment during a 21-day cycle on an oral contraceptive containing 3 mg NET-acetate and 0.05 mg ethinyloestradiol. Plasma non-protein bound concentrations of NET were determined by equilibrium dialysis. Sex hormone binding globulin (SHBG) was measured in all samples. An excellent correlation was found between plasma total, plasma non-protein bound and saliva levels of NET. Plasma non-protein bound and saliva concentrations were in the same range throughout, indicating that saliva concentrations reflect the free fraction of NET in plasma. SHBG increased considerably in all women. A slight decrease in the ratio between total and non-protein bound concentrations was found with time, possibly reflecting a slight increase in protein binding with increasing SHBG. The woman on anticonvulsant therapy had plasma total, plasma unbound and saliva NET concentrations that were only 30 per cent of those of the healthy women. The relationship between the different fractions was similar to that found in the healthy women. The non-protein bound fraction of NET was 4\p=n-\5 per cent of the total in all women studied.It is generally accepted that the pharmacologically active concentration of any given steroid is the fraction not bound to plasma proteins. In order to study the pharmacological activity and toxicity of a hormonal drug the determination of plasma nonprotein bound concentrations thus offers a more realistic opinion than the study of the total plasma concentrations of the drug. The estimation of the plasma non-protein bound fraction of a drug is usually carried out by equilibrium dialysis of plasma after determination of the total plasma concentrations by direct methods. Studies on diffe¬ rent drugs such as digoxin, phenytoin, and theophyllamine have shown that these substances are clearly detectable in the saliva and that the saliva concentrations reflect the non-protein bound frac¬ tion (Horning et al. 1977).In this study plasma and saliva concentrations of norethisterone (NET) were determined to calcu¬ late the degree of protein binding of NET and to find whether saliva NET concentrations could be used as a direct method to estimate the biologically active fraction of NET.

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Section: Discussionmentioning

confidence: 95%

“…Plasma and saliva concentrations of NET were deter¬ mined by a specific radioimmunoassay (Nygren et al 1974;Odlind et al 1979), with some modifications. The antiserum (gift from Schering AG, Berlin, W. Germany) was raised in rabbits immunized with NET 11-a-hemisuccinate bovine serum albumin.…”

Section: Radioimmunoassaysmentioning

confidence: 99%

Free norethisterone as reflected by saliva concentrations of norethisterone during oral contraceptive use

Odlind

Johansson

1981

Acta Endocrinologica

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“…To reject the null hypothesis, we estimated that 16 women would be required in each arm to detect a >40% intergroup difference in area under the curve with a 2-tailed alpha of 0.05 and 80% power. Our assumptions for the sample size calculation were based on a previously reported mean (standard deviation) NET area under the curve of 22.1 (10.9) ng·hr/mL after an oral dose of 0.3-mg NET 24. Peer-review literature does not specify minimum NET thresholds for contraceptive efficacy.…”

Section: Methodsmentioning

confidence: 99%

Effect of Protease Inhibitors on Steady-State Pharmacokinetics of Oral Norethindrone Contraception in HIV-Infected Women

Atrio¹,

Stanczyk²,

Neely³

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective Pharmacokinetic interactions exist between combined oral contraceptives and protease inhibitors (PI). However, such information is lacking for progestin-only oral contraception. We sought to define the steady-state pharmacokinetic interaction between norethindrone (NET) and PI in HIV infected women. Methods and design We conducted an open-label, prospective, non-randomized trial to characterize the steady-state pharmacokinetics of serum NET in HIVinfected women receiving PI compared to a control group of HIVinfected women receiving other non interacting drugs. Following 21 days of NET 0.35 mg ingestion once daily, serial serum samples were obtained at 0, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours. The area under the curve between 0 and 72 hours after ingestion was calculated by trapezoidal approximation. Results Thirty-five women were enrolled, two withdrew. Sixteen women in the PI group and 17 controls completed the study. NET half life, and maximum concentration were not significantly different between the two groups. Minimum concentration of NET was significantly higher in the PI group (p=0.01). The ratio of the geometric mean NET area under the curve in the PI group compared to controls was 1.5 (90% confidence interval 1.21-1.86). NET serum concentrations are significantly higher in HIVinfected women taking a PI compared to controls (p=0.004). Conclusions Co-administration of PI inhibits NET metabolism as shown by higher serum NET area under the curve levels, a surrogate marker for therapeutic contraceptive efficacy. This study supports increased utilization of progestin only pills in HIV infected women receiving certain PI regimens.

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“…Lynestrenol is a nonsteroidal compound metabolized to norethindrone [12], which is currently used in France to treat benign breast diseases [13]. Its mechanism of action is not completely known.…”

Section: Discussionmentioning

confidence: 99%

Progestin treatment depresses estrogen receptor but not cathepsin D levels in needle aspirates of benign breast disease

Maudelondé

Lavaud

Salazar

et al. 1991

Breast Cancer Res Tr

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We studied the effect of a progestin (lynestrenol) on estrogen receptors (ER) and cathepsin D (cath-D) levels immunochemically in successive fine needle aspirates of benign breast disease. Fibrocystic disease was the main pathology (43 out of 47 patients). Thirty-one patients were treated with 10 mg of lynestrenol daily from the fifth to the twenty-fifth day of the menstrual cycle for 1 to 3 months. Sixteen untreated patients were used as controls. Lynestrenol significantly decreased the percentage of ER stained cells. This is in agreement with the antiestrogenic effect of progestin and, for the first time, indicates that in vivo progestin may decrease the stimulatory effect of estrogens on mammary cells by decreasing their estrogen receptor content. No effect of progestin on cath-D level was found throughout the whole population. However, this level varied more between aspirates of each patient in the treated group than in the control group, suggesting heterogeneity in patient responses to progestin. Since cath-D may have a role in carcinogenesis, clinical follow-up of these patients and more detailed studies are required to determine whether this progestin-challenge test has any value for detecting high risk mastopathies and for predicting effectiveness of treatment.

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Plasma Levels of Norethindrone After Single Oral Dose Administration of Norethindrone and Lynestrenol

Cited by 33 publications

References 17 publications

Free norethisterone as reflected by saliva concentrations of norethisterone during oral contraceptive use

Free norethisterone as reflected by saliva concentrations of norethisterone during oral contraceptive use

Effect of Protease Inhibitors on Steady-State Pharmacokinetics of Oral Norethindrone Contraception in HIV-Infected Women

Progestin treatment depresses estrogen receptor but not cathepsin D levels in needle aspirates of benign breast disease

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