Pharmacokinetics and Tolerability of Lorcaserin in Special Populations: Elderly Patients and Patients with Renal or Hepatic Impairment

Abstract

PurposeTo 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. MethodsLorcaserin 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. FindingsIn elderly patients, Cmax was 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, Cmax was 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, Cmax was 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. ImplicationsBased 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.