Pharmacokinetics of Exogenous Natural and Synthetic Estrogens and Antiestrogens

Kuhnz, W.; Blode, Hartmut; Zimmermann, H.

doi:10.1007/978-3-642-60107-1_15

Cited by 31 publications

(33 citation statements)

References 304 publications

(244 reference statements)

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“…For this reason, studies often limit the duration of sampling to 24 h. Ideally, sampling should span over 4–5 half-lives of a drug [6, 7]. With a shorter sampling interval, estimates are used in combination with actual values to re-approximate the necessary time points for the area under the curve (AUC).…”

Section: Introductionmentioning

confidence: 99%

Prolonged monitoring of ethinyl estradiol and levonorgestrel levels confirms an altered pharmacokinetic profile in obese oral contraceptives users

et al. 2013

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Background Pharmacokinetic (PK) parameters based on short sampling times (48 h or less) may contain inaccuracies due to their dependency on extrapolated values. This study was designed to measure PK parameters with greater accuracy in obese users of a low-dose oral contraceptive (OC), and to correlate drug levels with assessments of end-organ activity. Study design Obese (BMI ≥30 kg/m2), ovulatory, otherwise healthy, women (n = 32) received an OC containing 20 mcg ethinyl estradiol (EE)/100 mcg levonorgestrel (LNG) for two cycles. EE and LNG PK parameters were characterized for 168 h at the end of Cycle 1. During Cycle 2, biweekly outpatient visits were performed to assess cervical mucus, monitor ovarian activity with transvaginal ultrasound, and obtain serum samples to measure EE, LNG, estradiol (E2), and progesterone (P) levels. PK parameters were calculated and correlated with end-organ activity and compared against control samples obtained from normal and obese women sampled up to 48 h in a previous study. Standard determination of PK accuracy was performed; defined by the dependency on extrapolated values (‘excess’ area under the curve of 25% or less). Results The mean BMI was 39.4 kg/m2 (SD 6.6) with a range of 30–64 kg/m2. Key LNG PK parameters were as follows: clearance 0.52 L/h (SD 0.24), half-life 65 h (SD 40), AUC 232 h*ng/mL (SD 102) and time to reach steady-state 13.6 days (SD 8.4). The majority of subjects had increased ovarian activity with diameter of follicles ≥8 mm (n = 25) but only seven women had follicles ≥10 mm plus cervical mucus scores ≥5. Evidence of poor end-organ suppression did not correlate with the severity of the alterations in PK. As compared to historical normal and obese controls (48 h PK sampling), clearance, half-life, area under the curve (AUC) and time to reach steady-state were found to be significantly different (p ≤ 0.05) in obese women undergoing a longer duration of PK sampling (168 h). Longer sampling also improved PK accuracy for obese women (excess AUC 20%) as compared to both normal and obese controls undergoing shorter sampling times (48 h) with excess AUCs of 25% and 50%, respectively. Conclusions Obesity results in significant alterations in OC steroid PK parameters but the severity of these alterations did not correlate with end-organ suppression. A longer PK sampling interval (168 h vs. 48 h) improved the accuracy of PK testing.

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Section: Introductionmentioning

confidence: 99%

Prolonged monitoring of ethinyl estradiol and levonorgestrel levels confirms an altered pharmacokinetic profile in obese oral contraceptives users

et al. 2013

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“…Although the pharmacokinetics of both E 2 V and DNG have been described previously [25][26][27][28] , the pharmacokinetic characteristics of these drugs following their administration as part of the OC regimen described above have not been investigated. The present study was carried out to evaluate the pharmacokinetics of this preparation in healthy women of fertile age.…”

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confidence: 99%

“…Following oral administration, E 2 V is rapidly hydrolysed as a result of metabolic processes in the gastrointestinal tract, intestinal wall and liver 25,26 . During this process, E 2 is further metabolised to oestrone (E 1 ) and oestrone sulphate (E 1 -S), which are the major metabolites of E 2 .…”

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confidence: 99%

Pharmacokinetics of an oral contraceptive containing oestradiol valerate and dienogest

Zeun

Uddin

et al. 2009

The European Journal of Contraception & Reproductive Health

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“…The PK differences in this study was likely blunted due to the shorter sampling scheme which was highlighted to be inadequate study design [15, 16] . Our research group has tested two dosing regimens in an effort to mitigate the obesity related PK changes [10] .…”

Section: Understanding Oc Pharmacokinetics (Pk) Could Reduce Failure mentioning

confidence: 99%

How can we improve oral contraceptive success in obese women?

Cherala

Edelman

2014

Expert Review of Clinical Pharmacology

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Summary A rapid increase in obesity rates worldwide further underscores the importance of better understanding the pharmacokinetic alterations in this sub-population and the subsequent effects on pharmaco-therapeutics. Pharmacokinetics of contraceptive steroids are altered in obese oral contraceptive users which may in turn impact efficacy. Our work has identified several dosing strategies that offset these pharmacokinetic changes and may improve effectiveness for obese OC users.

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Pharmacokinetics of Exogenous Natural and Synthetic Estrogens and Antiestrogens

Cited by 31 publications

References 304 publications

Prolonged monitoring of ethinyl estradiol and levonorgestrel levels confirms an altered pharmacokinetic profile in obese oral contraceptives users

Prolonged monitoring of ethinyl estradiol and levonorgestrel levels confirms an altered pharmacokinetic profile in obese oral contraceptives users

Pharmacokinetics of an oral contraceptive containing oestradiol valerate and dienogest

How can we improve oral contraceptive success in obese women?

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