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.
Keywords
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Article info
Publication history
Published online: December 31, 2016
Accepted:
December 27,
2016
Received in revised form:
December 13,
2016
Received:
June 20,
2016
Footnotes
☆Competing Interest Statement: C.L.W. is a paid consultant to Merck and Bayer, both of which manufacture oral contraceptives; however, not the oral contraceptive evaluated in this study. The remaining authors report no financial relationships with any organizations that might have an interest in the submitted work and no other relationships or activities that could appear to have influenced the submitted work.
☆☆Financial support: This pilot study was funded by the Howard Solomon Research Fund and an Irving Institute for Clinical and Translational Research (IICTR) Collaborative and Multidisciplinary Pilot Research (CaMPR) Award. The Biomarkers Core Laboratory of the IICTR supported the assays. M.C.P. is partially supported by the NCI under award number P30CA008748 (PI: C. Thompson) to Memorial Sloan Kettering Cancer Center. This study was also supported by the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through Grant Number UL1 TR000040, formerly the National Center for Research Resources, Grant Number UL1 RR024156. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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