Investigations of pharmacokinetics of levonorgestrel to specific consideration of a possible first-pass effect in women

Three women were each given 30 μg levonorgestrel in succession by the intravenous and oral routes. Another six women were given 150 μg levonorgestrel in the form of a MICROGYNON (R) coated tablet. Radiolabelled levonorgestrel was used for intravenous administration of 30 μg and oral administration of 150 μg. The plasma drug level was radioimmunoassayed after all treatments. In addition, after administration of levonorgestrel- 3H the course of total plasma radioactivity and elimination with urine and faeces were measured. After intravenous and oral administration, drug concentration and total plasma radioactivity declined in two disposition phases whose half-lives were in the range of 1– 1 2 hours and 1 day. In addition, after intravenous administration, an early phase with a half-life of about 10 min was observed. Absorption of levonorgestrel was rapid with a half-life of about 20 min. Orally administered doses were completely absorbed. It could be shown by means of an intra-individual comparison of the area under the drug level curve after intravenous and oral administration of the same dose that levonorgestrel is not subject to practically any first-pass effect.