Lorcaserin Hydrochloride

Selective serotonin type 2C (5-hydroxytryptamine [5-HT2C]) receptor agonist; anorexigenic agent.1 4 5 8 9

Absorption

Bioavailability

Absolute bioavailability not determined.1 Peak plasma concentrations attained approximately 1.5–2 hours following oral administration.1

Food

High-fat meal increased peak plasma concentrations by approximately 9% and AUC by approximately 5%, and delayed time to peak plasma concentration by approximately 1 hour.1

Special Populations

Mild hepatic impairment (Child-Pugh score 5–6): Lorcaserin peak plasma concentration decreased by 7.8%; AUC increased by 22%.1

Moderate hepatic impairment (Child-Pugh score 7–9): Lorcaserin peak plasma concentration decreased by 14.3%; AUC increased by 30%.1

Severe hepatic impairment: Pharmacokinetics not evaluated.1

Mild renal impairment (Clcr 50–80 mL/minute): Lorcaserin sulfamate (metabolite M1) exposure increased by 1.7-fold; N-carbamoyl-glucuronide lorcaserin (metabolite M5) exposure increased by 1.5-fold.1

Moderate renal impairment (Clcr 30–50 mL/minute): M1 exposure increased by 2.3-fold; M5 exposure increased by 2.5-fold.1

Severe renal impairment (Clcr <30 mL/minute): M1 exposure increased by 10.5-fold; M5 exposure increased by 5.1-fold.1 M1 and M5 accumulate.1

In patients with renal impairment, lorcaserin peak concentrations are decreased but AUC is unchanged.1

Distribution

Extent

Distributes into CSF and CNS.1

Plasma Protein Binding

Approximately 70%.1

Elimination

Metabolism

Extensively metabolized in the liver by multiple enzymatic pathways;1 6 7 major metabolites are inactive.1 M1 is the major circulating metabolite and M5 is the major metabolite in urine.1

Elimination Route

Excreted principally in urine (about 92%) as inactive metabolites.1 6

Half-life

Approximately 11 hours.1

Special Populations

Moderate hepatic impairment: Half-life of lorcaserin prolonged by 59%.1

Mild renal impairment: Half-life of M1 prolonged by 26%; half-life of M5 unchanged.1

Moderate renal impairment: Half-lives of M1 and M5 prolonged by 96 and 26%, respectively.1

Severe renal impairment: Half-lives of M1 and M5 prolonged by 508 and 22%, respectively.1

Hemodialysis: Standard 4-hour hemodialysis procedure removes approximately 18% of M5; does not remove lorcaserin or M1.1