Variation of Ethinylestradiol Blood Levels Among Healthy Women Using Oral Contraceptives

Stadel, Bruce V.; Sternthal, Phyllis M.; Schlesselman, James J.; Douglas, Margaret B.; Hall, W. Dallas; Kaul, Lalita; Ahluwalia, Balwant

doi:10.1016/s0015-0282(16)44589-9

Cited by 49 publications

(15 citation statements)

References 8 publications

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“…Plasma concentrations of EE and LNG were similar during all four monitored dosing intervals and were consistent with published data [30][31][32][33][34][35][36][37]. No individual displayed a consistent decrease in plasma concentration of either EE or LNG on the two study days.…”

Section: Resultssupporting

confidence: 89%

Lansoprazole does not affect the bioavailability of oral contraceptives.

Fuchs

Sennewald

Klotz

1994

Brit J Clinical Pharma

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The effects of the proton pump inhibitor lansoprazole on the bioavailability of a lowdose oral contraceptive (OC), containing 0.03 mg ethinyloestradiol (EE) and 0.15 mg levonorgestrel (LNG), were investigated. Twenty-four healthy females (aged 19-35 years; weight 60.6 ± 7.1 kg) participated in a multiple-dose, placebo-controlled, randomized two-way cross-over study. All subjects received the OC over 2 full menstrual cycles from day 1 to day 21 separated by a drug-free interval of 7 days. Lansoprazole (60 mg day-') or placebo was coadministered for 3 weeks each. Plasma concentrations of EE and LNG were determined by GC-MS. The 90% confidence intervals for ratios of Cmax and AUC after log transformation of both EE and LNG ranged between 91 and 111%, indicating that lansoprazole did not affect the bioavailability of EE and LNG.

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Section: Resultssupporting

confidence: 89%

Lansoprazole does not affect the bioavailability of oral contraceptives.

Fuchs

Sennewald

Klotz

1994

Brit J Clinical Pharma

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“…Unfortunately, ethinylestradiol levels could not be measured directly, because the blood was drawn at random during the 4‐week cycle of pill use in the MEGA study and without considering the hours after a pill was taken, which both have a significant influence on ethinylestradiol levels [7]. The hours after a pill was taken do not influence the SHBG levels, because of the half‐life of SHBG of ∼ 7 days.…”

Section: Mean Sex Hormone‐binding Globulin (Shbg) Levels and Adjustementioning

confidence: 99%

Effect of ethinylestradiol dose and progestagen in combined oral contraceptives on plasma sex hormone‐binding globulin levels in premenopausal women

Stegeman

Raps

Helmerhorst

et al. 2013

Journal of Thrombosis and Haemostasis

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“…Back et ai. There may be local factors that affect the plasma concentration profile of ethinyloestradiol, but Stadel et al (1980) found that 72% of the variation in plasma concentrations was probably due to genetic factors, and was unexplained by such factors as time since ingestion, day of the menstrual cycle, age, weight, blood pressure, cigarette and alcohol consumption. Plasma concentrations 12 to 24 hours after administration have been found to be in the range of 25 to 200 pg/ml (Kaufman et aI., 1981;Pasquaiini et aI., 1977;Verma et aI., 1975).…”

Section: Ethinyioestradiolmentioning

confidence: 99%

Clinical Pharmacokinetics of Oral Contraceptive Steroids

Orme

Back

Breckenridge

1983

Clinical Pharmacokinetics

159

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Oral contraceptive steroids are of 2 types: oestrogens, of which ethinyloestradiol is the most important, and progestagens, of which levonorgestrel and norethisterone are the most commonly used. All these steroids can be measured by a number of analytical techniques but there is little doubt that radioimmunoassay is the most convenient. All. the steroids are well absorbed in humans but while levonorgestrel is completely bioavailable, norethisterone has an average bioavailability of 70%. Ethinyloestradiol, too, is subject to presystemic metabolism with a mean bioavailability of 40 to 45%. The main site of presystemic metabolism is the gut wall, with the production of ethinyloestradiol sulphate. The progestagens norethynodrel, ethynodiol diacetate and lynoestrenol are quantitatively metabolised to norethisterone.The pharmacokinetics of the contraceptive steroids are best described by a 2-compartment open model. The terminal plasma half-life of levonorgestrel varies from 11 to 45 hours and of norethisterone from 5 to 14 hours. The Ii-phase half-life of ethinyloestradiol varies from 6 to 20 hours. The apparent volume of distribution of these contraceptive steroids (after intravenous administration) is between 1.5 and 4.3 Llkg. During long term treatment with oral contraceptive steroids, steady-state plasma concentrations of ethinyloestradiol (24 hours after administration) are between 10 and 200 pg/m!. Plasma concentrations of norethisterone and levonorgestrel at steady-state are higher than predicted from the single-dose kinetics because of enhanced binding of the progestagens following the induction of sex hormone binding globulin (SHBG) by ethinyloestradiol. Concentrations are in the range of 1.6 to 15.2 nglml for norethisterone and 0.8 to 4.5 nglml for levonorgestrel.All the contraceptive steroids are bound to proteins in plasma. Ethinyloestradiol is 97 to 98% bound to plasma albumin. The progestagens are bound both to albumin (levonorgestrel 93 to 95%; norethisterone 79 to 80%) and more specifically to SHBG. The binding capacity of SHBG can be enhanced by treatment with ethinyloestradiol or with more conventional enzyme-inducing drugs such as phenobarbitone, carbamazepine or rifampicin.Norethisterone and levonorgestrel are chiefly metabolised by reduction in the A ring and this is followed by conjugation with glucuronide or sulphate. The metabolism of levonorgestrel is stereoselective. Ethinyloestradiol is primarily hydroxylated at the 2 position but a wide variety of hydroxylated and methylated metabolites are formed and these are present both free and as glucuronide and sulphate conjugates. Ethinyloestradiol is conjugated directly at the 3 position (unlike the progestagens) and thus is liable to enterohepatic recirculation. Ethinyloestradiol sulphate concentrations in plasma are many times higher than that of the unchanged drug.

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Variation of Ethinylestradiol Blood Levels Among Healthy Women Using Oral Contraceptives

Cited by 49 publications

References 8 publications

Lansoprazole does not affect the bioavailability of oral contraceptives.

Lansoprazole does not affect the bioavailability of oral contraceptives.

Effect of ethinylestradiol dose and progestagen in combined oral contraceptives on plasma sex hormone‐binding globulin levels in premenopausal women

Clinical Pharmacokinetics of Oral Contraceptive Steroids

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