Estimating systemic exposure to levonorgestrel from an oral contraceptive

Area of Science:

• Pharmacokinetics
• Pharmacology
• Epidemiology

Background:

• The 24-hour steady-state area under the curve (AUC) is the gold standard for measuring oral contraceptive (OC) pharmacokinetics.
• Epidemiological studies often require simpler methods for pharmacokinetic assessment.

Purpose of the Study:

• To evaluate if limited sampling at steady state or after single/few OC doses can serve as a proxy for the progestin 24-hour steady-state AUC.
• To determine the feasibility of using simplified pharmacokinetic measures in large-scale pharmaco-epidemiologic studies.

Main Methods:

• A 13-sample, 24-hour pharmacokinetic study was conducted on day 1 and day 21 of the first cycle of a monophasic OC (30 mcg ethinyl estradiol/150 mcg levonorgestrel).
• A single-dose, 9-sample study was performed after a 1-month washout period.
• Steady-state results were compared with various simplified steady-state and single-dose sampling schemes.

Main Results:

• The 13-sample steady-state 24-hour levonorgestrel (LNG) AUC showed high correlation with the steady-state 24-hour trough value (r=0.95) and steady-state 6-, 8-, 12-, and 16-hour values (0.92≤r≤0.95).
• Trough values after one or two OC doses moderately correlated with the steady-state 24-hour AUC (r=0.70 and r=0.77, respectively).

Conclusions:

• Single time-point LNG concentrations at steady state are excellent proxies for complete AUC measurements.
• Trough levels after two single OC doses serve as fair proxies for steady-state AUC.
• These findings offer practical tools for large studies investigating the relationship between systemic LNG exposure and OC side effects.