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

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...

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Autores principales: Nave, Rüdiger, Klein, Stefan, Müller, André, Chang, Xinying, Höchel, Joachim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763360/
https://www.ncbi.nlm.nih.gov/pubmed/28783867
http://dx.doi.org/10.1002/jcph.984
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author Nave, Rüdiger
Klein, Stefan
Müller, André
Chang, Xinying
Höchel, Joachim
author_facet Nave, Rüdiger
Klein, Stefan
Müller, André
Chang, Xinying
Höchel, Joachim
author_sort Nave, Rüdiger
collection PubMed
description 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 (C(av,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 C(av,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.
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spelling pubmed-57633602018-01-17 Absence of Effect of Intravaginal Miconazole, Clindamycin, Nonoxynol‐9, and Tampons on the Pharmacokinetics of an Anastrozole/Levonorgestrel Intravaginal Ring Nave, Rüdiger Klein, Stefan Müller, André Chang, Xinying Höchel, Joachim J Clin Pharmacol Women's Health 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 (C(av,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 C(av,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. John Wiley and Sons Inc. 2017-08-07 2018-01 /pmc/articles/PMC5763360/ /pubmed/28783867 http://dx.doi.org/10.1002/jcph.984 Text en © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Women's Health
Nave, Rüdiger
Klein, Stefan
Müller, André
Chang, Xinying
Höchel, Joachim
Absence of Effect of Intravaginal Miconazole, Clindamycin, Nonoxynol‐9, and Tampons on the Pharmacokinetics of an Anastrozole/Levonorgestrel Intravaginal Ring
title Absence of Effect of Intravaginal Miconazole, Clindamycin, Nonoxynol‐9, and Tampons on the Pharmacokinetics of an Anastrozole/Levonorgestrel Intravaginal Ring
title_full Absence of Effect of Intravaginal Miconazole, Clindamycin, Nonoxynol‐9, and Tampons on the Pharmacokinetics of an Anastrozole/Levonorgestrel Intravaginal Ring
title_fullStr Absence of Effect of Intravaginal Miconazole, Clindamycin, Nonoxynol‐9, and Tampons on the Pharmacokinetics of an Anastrozole/Levonorgestrel Intravaginal Ring
title_full_unstemmed Absence of Effect of Intravaginal Miconazole, Clindamycin, Nonoxynol‐9, and Tampons on the Pharmacokinetics of an Anastrozole/Levonorgestrel Intravaginal Ring
title_short Absence of Effect of Intravaginal Miconazole, Clindamycin, Nonoxynol‐9, and Tampons on the Pharmacokinetics of an Anastrozole/Levonorgestrel Intravaginal Ring
title_sort absence of effect of intravaginal miconazole, clindamycin, nonoxynol‐9, and tampons on the pharmacokinetics of an anastrozole/levonorgestrel intravaginal ring
topic Women's Health
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763360/
https://www.ncbi.nlm.nih.gov/pubmed/28783867
http://dx.doi.org/10.1002/jcph.984
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