Influence of changes in the concentration of sex hormone-binding globulin in human serum on the protein binding of the contraceptive steroids levonorgestrel, 3-keto-desogestrel and gestodene

Kuhnz, W.; Schütt, Barbara; Woloszczak, Rolf

doi:10.1016/0960-0760(94)90211-9

Cited by 12 publications

(11 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For the population PK model for LNG, plasma concentrations of LNG and serum concentrations of SHBG as well as residual content measurements of LNG in the IVRs were used. SHBG data were included due to the interaction of LNG with SHBG, ie, binding of LNG to SHBG and inhibitive effect of LNG on SHBG synthesis …”

Section: Methodsmentioning

confidence: 99%

Model‐Based Dose Selection for Intravaginal Ring Formulations Releasing Anastrozole and Levonorgestrel Intended for the Treatment of Endometriosis Symptoms

Reinecke

Schultze‐Mosgau

Nave

et al. 2016

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Pharmacokinetics (PK) of anastrozole (ATZ) and levonorgestrel (LNG) released from an intravaginal ring (IVR) intended to treat endometriosis symptoms were characterized, and the exposure-response relationship focusing on the development of large ovarian follicle-like structures was investigated by modeling and simulation to support dose selection for further studies. A population PK analysis and simulations were performed for ATZ and LNG based on clinical phase 1 study data from 66 healthy women. A PK/PD model was developed to predict the probability of a maximum follicle size ≥30 mm and the potential contribution of ATZ beside the known LNG effects. Population PK models for ATZ and LNG were established where the interaction of LNG with sex hormone-binding globulin (SHBG) as well as a stimulating effect of estradiol on SHBG were considered. Furthermore, simulations showed that doses of 40 μg/d LNG combined with 300, 600, or 1050 μg/d ATZ reached anticipated exposure levels for both drugs, facilitating selection of ATZ and LNG doses in the phase 2 dose-finding study. The main driver for the effect on maximum follicle size appears to be unbound LNG exposure. A 50% probability of maximum follicle size ≥30 mm was estimated for 40 μg/d LNG based on the exposure-response analysis. ATZ in the dose range investigated does not increase the risk for ovarian cysts as occurs with LNG at a dose that does not inhibit ovulation.

show abstract

Section: Methodsmentioning

confidence: 99%

Model‐Based Dose Selection for Intravaginal Ring Formulations Releasing Anastrozole and Levonorgestrel Intended for the Treatment of Endometriosis Symptoms

Reinecke

Schultze‐Mosgau

Nave

et al. 2016

The Journal of Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…In this context, SHBG concentrations should be considered because of the interaction of LNG with SHBG and because SHBG is a major binding protein for LNG . The geometric mean SHBG concentrations for this period were comparable in all treatment groups as well as on day 20 (group D).…”

Section: Discussionmentioning

confidence: 97%

“…Sex hormone‐binding globulin (SHBG) data are of interest because of the interaction of LNG with SHBG, that is, the binding of LNG to SHBG and the inhibitive effect of LNG on SHBG synthesis …”

Section: Methodsmentioning

confidence: 99%

Absence of Effect of Intravaginal Miconazole, Clindamycin, Nonoxynol‐9, and Tampons on the Pharmacokinetics of an Anastrozole/Levonorgestrel Intravaginal Ring

Nave

Klein

Müller

et al. 2017

The Journal of Clinical Pharma

View full text Add to dashboard Cite

A study was performed to investigate the effect of an intravaginally administered antimycotic, an antibiotic, and a spermicide plus the co‐usage of tampons on the pharmacokinetics (PK) of levonorgestrel (LNG) and anastrozole (ATZ) administered as an intravaginal ring (IVR) releasing 1050 μg ATZ per day and 40 μg LNG per day. In this parallel‐group, randomized, open‐label study, healthy premenopausal women received an IVR as the main treatment. Comedications were administered on 3 consecutive evenings during treatment with IVR on days 9–11 (group A, 400 mg miconazole; group B, 100 mg clindamycin; group C, 75 mg nonoxynol‐9); tampon co‐usage (group D) was performed on days 20–23. The primary PK parameter was the average plasma concentration (Cav,ss) of ATZ and LNG at defined intervals, mainly prior to, during, and up to 7 days after the start of comedication. Fifty‐two subjects were included, and at least 11 subjects per group completed the treatments. Overall, the medications and comedications were safe and well tolerated. Very similar ATZ and LNG plasma levels were observed across all groups. The calculated ratios of Cav,ss confirmed the absence of PK interactions because all relevant point estimates and 90% confidence intervals were within the range of 0.800–1.250, which is typically used in bioequivalence studies. These results demonstrate the absence of PK interactions between ATZ/LNG released from IVR and the tested antibiotic, antimycotic, spermicide, and tampons. Therefore, no restrictions for the use of the IVR are needed to continue the clinical program intended to treat endometriosis symptoms.

show abstract

“…Daneben wird auch die Synthese steroidtransportierender Globuline wie SHBG und CBG aktiviert [20]. Dies soll hier nicht weiter ausgeführt werden, da dem ein eigenes Kapitel in dem vorliegenden Heft gewidmet ist.…”

Section: Synthetische Steroide In Oralen Kontrazeptivaunclassified

“…Ethinylestradiol selbst wird kaum an SHBG gebunden, in unterschiedlichem Maûe jedoch andere Steroide und hierbei auch die synthetischen Gestagene, was sich zum einen auf die Halbwertszeit der Gestagene auswirken kann, zum anderen zusätzliche indirekte Wirkungen zur Folge haben kann [20]. Ethinylestradiol selbst wird kaum an SHBG gebunden, in unterschiedlichem Maûe jedoch andere Steroide und hierbei auch die synthetischen Gestagene, was sich zum einen auf die Halbwertszeit der Gestagene auswirken kann, zum anderen zusätzliche indirekte Wirkungen zur Folge haben kann [20].…”

Section: Synthetische Steroide In Oralen Kontrazeptivaunclassified

Hormonale Kontrazeption

1998

View full text Add to dashboard Cite

Influence of changes in the concentration of sex hormone-binding globulin in human serum on the protein binding of the contraceptive steroids levonorgestrel, 3-keto-desogestrel and gestodene

Cited by 12 publications

References 15 publications

Model‐Based Dose Selection for Intravaginal Ring Formulations Releasing Anastrozole and Levonorgestrel Intended for the Treatment of Endometriosis Symptoms

Model‐Based Dose Selection for Intravaginal Ring Formulations Releasing Anastrozole and Levonorgestrel Intended for the Treatment of Endometriosis Symptoms

Absence of Effect of Intravaginal Miconazole, Clindamycin, Nonoxynol‐9, and Tampons on the Pharmacokinetics of an Anastrozole/Levonorgestrel Intravaginal Ring

Hormonale Kontrazeption

Contact Info

Product

Resources

About