Levonorgestrel. Clinical pharmacokinetics

Area of Science:

• Pharmacology and Drug Metabolism
• Endocrinology

Background:

• Levonorgestrel is a widely used progestogen, often administered alone or with ethinylestradiol.
• Understanding its pharmacokinetics is crucial for optimizing therapeutic efficacy and safety.
• Existing data show considerable variability in levonorgestrel serum concentrations and pharmacokinetic parameters.

Purpose of the Study:

• To review published data on serum concentrations and pharmacokinetic parameters of levonorgestrel.
• To identify factors contributing to inter- and intra-individual variability in levonorgestrel pharmacokinetics.

Main Methods:

• Systematic review of published studies on levonorgestrel pharmacokinetics.
• Inclusion of data from various administration routes (oral, subcutaneous, intravaginal, intra-uterine).
• Analysis of pharmacokinetic parameters and serum concentrations reported in the literature.

Main Results:

• Significant variability observed in levonorgestrel serum concentrations and pharmacokinetic parameters across studies.
• Large interindividual variability in levonorgestrel pharmacokinetics is consistently demonstrated.
• Sex hormone binding globulin (SHBG) plays a role due to strong binding and SHBG level influences, but does not explain all variability.

Conclusions:

• The factors responsible for the substantial inter- and intra-individual variability in levonorgestrel pharmacokinetics are not fully elucidated.
• While sex hormone binding globulin (SHBG) is implicated, it does not account for all observed anomalies in levonorgestrel metabolism.
• Further research is needed to identify all factors influencing levonorgestrel pharmacokinetics.