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Comparative Study
. 2020 Dec;25(6):417-426.
doi: 10.1080/13625187.2020.1815008. Epub 2020 Oct 2.

Comparative pharmacokinetic analysis of levonorgestrel-releasing intrauterine systems and levonorgestrel-containing contraceptives with oral or subdermal administration route

Birte Maria Hofmann  1 , Dan Apter  2 , Johannes Bitzer  3 , Isabel Reinecke  4 , Marco Serrani  5 , Joachim Höchel  1 , Martin Merz  5
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Free article
Comparative Study

Comparative pharmacokinetic analysis of levonorgestrel-releasing intrauterine systems and levonorgestrel-containing contraceptives with oral or subdermal administration route

Birte Maria Hofmann et al. Eur J Contracept Reprod Health Care. 2020 Dec.
Free article

Abstract

Objective: To compare systemic exposure to levonorgestrel (LNG) released from commercially available intrauterine systems (IUSs), a subdermal implant, and oral contraceptives.

Methods: An integrated population pharmacokinetic (popPK) analysis of data from over 3400 individuals in ten clinical studies with six different LNG-releasing contraceptives (four long-acting reversible contraceptives [LARCs: LNG-IUS 8, 12, and 20, initially releasing LNG 14, 17.5, and 20 μg/day, a subdermal implant initially releasing LNG 100 μg/day according to label]; progestin-only pill [POP: LNG 30 μg/day]; and combined oral contraceptive [COC] pill [LNG 100 μg/day and ethinylestradiol 20 μg/day]), was conducted to generate a popPK model. LNG release rates, and total and unbound serum/plasma LNG concentrations with LARCs were estimated over the indicated period of use; maximum (Cmax) and average (Cav) serum LNG concentrations were estimated at steady state for oral contraceptives. Influence of body weight on LNG PK was also investigated.

Results: Serum LNG concentration with LARCs increased with increasing daily LNG release rate, being lowest with LNG-IUS 8, higher with LNG-IUS 12 and LNG-IUS 20, and highest with the subdermal implant (1.7-2.1-times that with LNG-IUS 20). Compared with early serum LNG concentrations with LNG-IUS 20, Cav and Cmax were 1.7- and 4.5-fold higher with POP, and 8.6- and 18-fold higher with COC. Total LNG bioavailability was >97% for the LNG-IUSs and 66-80% with other contraceptives. Serum/plasma LNG concentrations decreased with increasing body weight.

Conclusions: Among the contraceptives examined, COC had the highest and LNG-IUSs the lowest systemic exposure to LNG. Systemic LNG concentration was inversely correlated to body weight.

Keywords: Contraception; levonorgestrel; levonorgestrel-releasing contraceptive system; pharmacokinetics.

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