Flibanserin

Pharmacological Actions and Their Influence
Flibanserin’s pharmacological profile is characterized by its interactions with serotonin and dopamine receptors, which are central to its therapeutic effects in HSDD. It acts as an agonist at 5-HT1A receptors, with a high binding affinity (Ki = 1 nM in human cells, as per IUPHAR/BPS Guide to PHARMACOLOGY: flibanserin), and an antagonist at 5-HT2A receptors (Ki = 49 nM, from the same source). Additionally, it exhibits antagonist or weak partial agonist activity at dopamine D4 receptors (Ki = 4-24 nM, as noted in Flibanserin - Wikipedia), with lower affinities for 5-HT2B (Ki = 89.3 nM) and 5-HT2C (Ki = 88.3 nM) receptors, where it acts as an antagonist Flibanserin - Wikipedia.
These interactions lead to a reduction in serotonin levels and an increase in dopamine and norepinephrine in the brain, particularly in the prefrontal cortex, which is thought to enhance sexual desire and reduce distress associated with HSDD Multifunctional Pharmacology of Flibanserin: Possible Mechanism of Therapeutic Action in Hypoactive Sexual Desire Disorder | ScienceDirect. The onset of effect was observed from the first measurement point after 4 weeks of treatment, with effects maintained throughout the treatment period, as evaluated in three phase 3 clinical trials Flibanserin - Wikipedia.
Specific values for the time course of these actions include a Tmax of 0.75 hours (range 0.75-4.0 hours), indicating rapid absorption and peak plasma concentration, with a half-life of approximately 11 hours influencing the duration of action Fda. The EC50 for agonist activity at 5-HT1A receptors is approximately 630.96 nM, suggesting the concentration needed for half-maximal effect in certain functional assays IUPHAR/BPS Guide to PHARMACOLOGY: flibanserin.
Half-Life and Bioavailabilities
The half-life of Flibanserin is consistently reported as approximately 11 hours across multiple sources, including the FDA label Fda, indicating the time required for the plasma concentration to reduce by half, which is crucial for determining dosing intervals. Its oral bioavailability is 33%, meaning only about a third of the ingested dose is absorbed systemically, a factor influenced by first-pass metabolism primarily via CYP3A4, with lesser involvement of CYP2C19 Flibanserin: Uses, Interactions, Mechanism of Action | DrugBank Online. Other routes of administration, such as intravenous, are not clinically relevant for Flibanserin, so additional bioavailability data are not available.
Dosage Details
The recommended dosage for Flibanserin is 100 mg once daily at bedtime, as per the FDA label Fda, which is also considered the minimum effective dose based on clinical trials where lower doses (e.g., 50 mg twice daily) were less effective Flibanserin - Wikipedia. The maximum safe dose is generally 100 mg, with higher doses not recommended due to increased risk of adverse effects, as evidenced by clinical development where doses above 250 mg were not tolerated by adults Accidental Flibanserin Ingestion in Children Causing Acute Respiratory and Central Nervous System Depression | PMC.
Case reports of accidental ingestion in children provide insight into the effects of higher doses. For instance, doses ranging from 400 mg to 1500 mg (4 to 15 tablets of 100 mg each) led to severe symptoms such as ataxia, somnolence, respiratory depression, and CNS depression, requiring intubation in some cases, but all recovered within a few days with supportive care Accidental Flibanserin Ingestion in Children Causing Acute Respiratory and Central Nervous System Depression | PMC. This suggests that while high doses are dangerous, they are not necessarily lethal, though the LD50 for humans is not publicly available.
The safe range is thus 100 mg daily, with the FDA contraindicating use with alcohol, moderate/strong CYP3A4 inhibitors, and in hepatic impairment due to increased risk of hypotension and syncope Fda. The estimation of when it starts to become too dangerous aligns with doses above 100 mg, particularly given the narrow safety margin and reports of severe effects at higher doses.