Levoplant Mechanism of Action

Pharmacotherapeutic group: Progestogens, levonorgestrel.
Pharmacology: Pharmacodynamics: The active ingredient in Levonorgestrel (Levoplant), levonorgestrel, is a synthetic progestin. The primary pharmacologic action of levonorgestrel is its anti-fertility effect. Levonorgestrel has been shown to affect ovarian function in various ways. This ranges from: the absence of follicular and luteal activity through to normal follicular activity but deficient luteal activity to normal ovulatory patterns. Levonorgestrel causes thickening of the cervical mucus, thus preventing the passage of spermatozoa into the uterus. It also suppresses the endometrium and may prevent implantation of the blastocyst.
Pharmacokinetics: Absorption: Levonorgestrel is released from the Levonorgestrel (Levoplant) directly into tissue fluid. Maximum plasma levonorgestrel concentrations of approximately 833 ± 367 pg/mL are reached about 5.4 days after insertion. After the initial phase, levonorgestrel concentrations decline to 430 ± 205 pg/mL within one month, 351 ± 210 pg/mL within six months, 311 ± 197 pg/mL within one year. Plasma levonorgestrel concentrations are inversely related to body weight. However, due to the great variation in plasma levonorgestrel concentrations and in individual response, plasma concentrations alone are not predictive of the risk of pregnancy in an individual woman. Considerable inter- and intra-individual variation occurs, and serum drug concentrations are affected by individual clearance rates and body weight, among other factors. In Levonorgestrel (Levoplant) users, plasma levonorgestrel concentrations are substantially below those observed in women taking oral contraceptives containing levonorgestrel.
Distribution: Levonorgestrel in serum is primarily protein bound. Approximately half is bound to sex hormone binding globulin (SHBG) and half to albumin. SHBG concentrations are depressed by levonorgestrel within a few days of administration, with resultant decreases in circulating levonorgestrel concentrations.
Metabolism: Levonorgestrel metabolic pathways have been only partially delineated. 16β-hydroxylation is an identified pathway of metabolism. Concentrations of metabolites in circulation soon exceed those of levonorgestrel, mostly as conjugated sulfates. Metabolic clearance rates may differ among individuals by several fold, which is believed to account also in part for the wide variation observed in levonorgestrel serum concentrations among implant users.
Excretion: The elimination half-life of levonorgestrel is approximately 13 to 18 hours. Levonorgestrel and its metabolites are primarily excreted in the urine (40% to 68%) and about 16% to 48% are excreted in feces. After removal of the implants, levonorgestrel concentrations decrease below 100 pg/mL by 96 hours and below sensitivity of the assay by 5 days to 2 weeks.