Estimating Systemic Exposure to Levonorgestrel from an Oral Contraceptive

Overview

Journal Contraception

Publisher Elsevier

Specialty Reproductive Medicine

Date 2017 Jan 3

PMID 28041990

Citations 9

Authors

Cale N Basaraba

Carolyn L Westhoff

Malcolm C Pike

Renu Nandakumar

Serge Cremers

Affiliations

Soon will be listed here.

Abstract

Objective: The gold standard for measuring oral contraceptive (OC) pharmacokinetics is the 24-h steady-state area under the curve (AUC). We conducted this study to assess whether limited sampling at steady state or measurements following use of one or two OCs could provide an adequate proxy in epidemiological studies for the progestin 24-h steady-state AUC of a particular OC.

Study Design: We conducted a 13-sample, 24-h pharmacokinetic study on both day 1 and day 21 of the first cycle of a monophasic OC containing 30-mcg ethinyl estradiol and 150-mcg levonorgestrel (LNG) in 17 normal-weight healthy White women and a single-dose 9-sample study of the same OC after a 1-month washout. We compared the 13-sample steady-state results with several steady-state and single-dose results calculated using parsimonious sampling schemes.

Results: The 13-sample steady-state 24-h LNG AUC was highly correlated with the steady-state 24-h trough value [r=0.95; 95% confidence interval (0.85, 0.98)] and with the steady-state 6-, 8-, 12- and 16-h values (0.92≤r≤0.95). The trough values after one or two doses were moderately correlated with the steady-state 24-h AUC value [r=0.70; 95% CI (0.27, 0.90) and 0.77; 95% CI (0.40, 0.92), respectively].

Conclusions: Single time-point concentrations at steady state and after administration of one or two OCs gave highly to moderately correlated estimates of steady-state LNG AUC. Using such measures could facilitate prospective pharmaco-epidemiologic studies of the OC and its side effects.

Implications: A single time-point LNG concentration at steady state is an excellent proxy for complete and resource-intensive steady-state AUC measurement. The trough level after two single doses is a fair proxy for steady-state AUC. These results provide practical tools to facilitate large studies to investigate the relationship between systemic LNG exposure and side effects in a real-life setting.

Citing Articles

Validation of 24-hour trough concentration as a proxy for intensive pharmacokinetic measurements for a combined oral contraceptive pill containing desogestrel.

Lazorwitz A, Sheeder J Contraception. 2023; 126:110093.

PMID: 37331464 PMC: 10528283. DOI: 10.1016/j.contraception.2023.110093.

Combined and progestagen-only hormonal contraceptives and breast cancer risk: A UK nested case-control study and meta-analysis.

Fitzpatrick D, Pirie K, Reeves G, Green J, Beral V PLoS Med. 2023; 20(3):e1004188.

PMID: 36943819 PMC: 10030023. DOI: 10.1371/journal.pmed.1004188.

The progesterone-receptor modulator, ulipristal acetate, drastically lowers breast cell proliferation.

Westhoff C, Guo H, Wang Z, Hibshoosh H, Polaneczky M, Pike M Breast Cancer Res Treat. 2022; 192(2):321-329.

PMID: 35015210 PMC: 10088437. DOI: 10.1007/s10549-021-06503-1.

Pharmacokinetics, metabolism and serum concentrations of progestins used in contraception.

Bick A, Louw-du Toit R, Skosana S, Africander D, Hapgood J Pharmacol Ther. 2020; 222:107789.

PMID: 33316287 PMC: 8122039. DOI: 10.1016/j.pharmthera.2020.107789.

Atogepant Has No Clinically Relevant Effects on the Pharmacokinetics of an Ethinyl Estradiol/Levonorgestrel Oral Contraceptive in Healthy Female Participants.

Ankrom W, Xu J, Vallee M, Dockendorf M, Armas D, Boinpally R J Clin Pharmacol. 2020; 60(9):1157-1165.

PMID: 32297990 PMC: 7496689. DOI: 10.1002/jcph.1610.

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