title: Pharmacokinetics and Tolerability of Lorcaserin in Special Populations: Elderly Patients and Patients with Renal or Hepatic Impairment.
abstract: OBJECTIVE
  To determine whether dosage adjustment is likely to be necessary for effective and well-tolerated use of a pharmaceutical agent, guidance documents from the US Food and Drug Administration recommend pharmacokinetics studies in patients with impaired renal or impaired hepatic function and in the elderly population. Three studies were conducted to evaluate the pharmacokinetic properties and tolerability of lorcaserin in these populations.
  
  
  METHODS
  Lorcaserin was evaluated in single-dose pharmacokinetics studies of 3 overweight/obese populations: (1) elderly (aged >65 years) patients; (2) patients with impaired renal function; and (3) those with impaired hepatic function.
  
  
  RESULTS
  In elderly patients, Cmaxwas lower (geometric mean ratio [GMR], 0.83; 90% CI, 0.71-0.97), but AUC was unchanged versus adult patients. In patients with renal impairment, Cmaxwas reduced versus that in patients with normal renal function (GMR: mild impairment, 0.99 [90% CI, 0.76-1.29]; moderate, 0.70 [90% CI, 0.54-0.90]; and severe, 0.69 [90% CI, 0.53-0.89]); no trend in AUC was observed in this group versus renal impairment. In patients with hepatic impairment, Cmaxwas decreased (GMR: mild impairment, 0.92 [90% CI, 0.76-1.11]; moderate, 0.86 [90% CI, 0.71-1.04]), and AUC was increased versus patients with normal hepatic function.
  
  
  CONCLUSIONS
  Based on these findings, no lorcaserin dose adjustments are necessary in elderly patients with normal renal function or in patients with mild/moderate renal or hepatic impairment. ClinicalTrials.gov identifiers: NCT00828581, NCT00828438, and NCT00828932.
authors.affiliation: Arena Pharmaceuticals, San Diego, California. Electronic address: rchristopher@arenapharm.com.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Christopher
authors.affiliation: Arena Pharmaceuticals, San Diego, California.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Morgan
authors.affiliation: Arena Pharmaceuticals, San Diego, California.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Christen M. Anderson Consulting, San Diego, California.
authors.forename: Christen
authors.initials: C
authors.lastname: Anderson
authors.affiliation: Arena Pharmaceuticals, San Diego, California; Sanchez Kam, LLC, Alexandria, Virginia.
authors.forename: Matilde
authors.initials: M
authors.lastname: Sanchez
authors.affiliation: Arena Pharmaceuticals, San Diego, California.
authors.forename: William
authors.initials: W
authors.lastname: Shanahan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000188:drug therapy / Q000378:metabolism*; D055815:Young Adult
chemical_list: D019440:Anti-Obesity Agents; D001552:Benzazepines; C506658:lorcaserin
keywords: agonist; elderly; hepatic; obesity; pharmacodynamics; pharmacokinetics; receptor; renal; serotonin; weight loss