The Pharmacokinetics of Levonorgestrel (Plan B and Generics)
Levonorgestrel is the active ingredient in common over-the-counter emergency contraceptive pills like Plan B One-Step, Take Action, and My Way. Understanding its pharmacokinetics—how the body absorbs, distributes, metabolizes, and excretes the drug—is key to knowing how long it stays in the system.
Absorption and Metabolism
After being taken orally, levonorgestrel is quickly and completely absorbed. It is then extensively metabolized in the liver, primarily through the cytochrome P450 (CYP) 3A4 enzyme pathway. This metabolic process breaks down the hormone into various metabolites, which are eventually prepared for elimination.
Half-Life and Excretion
The mean elimination half-life of levonorgestrel is approximately 24 to 27 hours. This means that half of the drug's concentration is eliminated from the body within that timeframe. The body continues to process the remaining drug in subsequent half-life cycles. The excretion process occurs through both urine and feces, with about 45% eliminated through urine and 32% through feces. While the most potent effects occur in the first day or so, the drug is not fully cleared from the system until around five half-lives have passed, which amounts to approximately 5 to 6 days. It is important to remember that residual amounts remaining in the body beyond the peak effectiveness window do not continue to provide contraception.
The Pharmacokinetics of Ulipristal Acetate (Ella)
Ulipristal acetate, sold under the brand name Ella, is another type of emergency contraceptive that requires a prescription. Its clearance timeline is somewhat different from that of levonorgestrel.
Absorption and Metabolism
Ulipristal acetate is also absorbed rapidly after oral ingestion. It is then extensively metabolized in the liver, mainly by the CYP3A4 enzyme, into both active and inactive metabolites. The drug's absorption can be affected by food; for instance, a high-fat meal can delay the time it takes to reach maximum concentration.
Half-Life and Excretion
The terminal half-life of ulipristal acetate is approximately 32 hours. A key difference in its clearance is the primary route of elimination, which is through the feces, with less than 10% excreted in the urine. Given its half-life, the medication can remain in the system for about a week before being completely cleared. This longer half-life contributes to its wider effective window of up to five days after unprotected sex.
Factors Influencing Emergency Contraceptive Clearance
Several individual factors can affect how quickly or slowly an emergency contraceptive is cleared from the body. These can cause some variability in the clearance timeline for different people.
- Individual Metabolism: The efficiency of liver enzymes, particularly CYP3A4, can vary from person to person due to genetics. Those with a faster metabolism may clear the drug more quickly.
- Drug Interactions: Certain medications and herbal supplements can interfere with the CYP3A4 pathway, affecting the metabolism of ECPs. Potent enzyme-inducing drugs (like St. John's wort, rifampicin, and some anticonvulsants) can increase the clearance rate and reduce the ECP's effectiveness. Conversely, CYP3A4 inhibitors could potentially slow clearance.
- Body Weight: Some studies have shown that levonorgestrel may be less effective in people with higher body mass index (BMI), although data regarding its effect on clearance time is inconclusive. Ulipristal acetate may also have reduced efficacy in heavier individuals, but the effect on clearance is not clearly established.
- Liver Function: Since both drugs are metabolized in the liver, impaired liver function can significantly slow down the clearance of the medication from the body.
Comparison of Emergency Contraceptive Pills
| Feature | Levonorgestrel (Plan B, Generics) | Ulipristal Acetate (Ella) |
|---|---|---|
| Active Ingredient | Levonorgestrel 1.5 mg | Ulipristal acetate 30 mg |
| Availability | Over-the-counter, no prescription needed | Prescription required |
| Effectiveness Window | Up to 72 hours (3 days) after unprotected sex | Up to 120 hours (5 days) after unprotected sex |
| Half-Life | ~27 hours | ~32 hours |
| Primary Clearance Route | Urine and feces | Primarily feces |
| Action on Ovulation | Delays or inhibits ovulation before the LH surge | Delays or inhibits ovulation even during the LH surge |
| Post-Effectiveness Period | Can resume hormonal birth control immediately after taking | Wait 5 days before starting/resuming hormonal birth control |
The Difference Between Duration in Body and Effectiveness
One of the most common misconceptions about emergency contraception is that the pills remain effective for as long as the hormones are detectable in the body. The contraceptive effect is not tied to the total time the drug is present. Instead, it relies on disrupting the ovulation process, which is a temporary effect that must occur within a specific window. The sooner the pill is taken, the more effective it is at preventing the release of an egg. Once ovulation has occurred, the pill is no longer able to prevent pregnancy.
Conclusion
Emergency contraceptive pills, containing either levonorgestrel or ulipristal acetate, are cleared from the body within a matter of days, not weeks or months. Levonorgestrel has a shorter half-life and is mostly gone in 5 to 6 days, while ulipristal acetate takes about a week to clear. However, this clearance time is much longer than the window of effectiveness for preventing pregnancy, which is most critical in the first few days after unprotected sex. Individual factors, including metabolism and drug interactions, can influence the exact clearance timeline. It is crucial to understand these differences and use ECPs as intended—for emergency purposes—and to discuss long-term contraceptive options with a healthcare provider.
For more information on emergency contraception, you can consult the Centers for Disease Control and Prevention (CDC)(https://www.cdc.gov/contraception/hcp/usspr/emergency-contraception.html).
