title: Pharmacokinetics, tolerability, and safety of ACP-103 following single or multiple oral dose administration in healthy volunteers.
abstract: The pharmacokinetics, safety, and tolerability of ACP-103, a selective serotonin 5-HT(2A) receptor inverse agonist, were evaluated in 2 double-blind, placebo-controlled, dose escalation studies in healthy male volunteers. Pharmacokinetic sampling was measured up to 216 hours after single oral/nasogastric doses of ACP-103 and after the last dose of once-daily oral administration of ACP-103 for 14 days. Single doses of ACP-103 (20-300 mg) resulted in dose-proportionate mean C(max) values (9-152 ng/mL) and AUC(0-infinity) (706-10 798 h x ng/mL), and multiple doses (50-150 mg) resulted in dose-proportionate mean C(max,ss) (93-248 ng/mL) and AUC(0-infinity,ss) (1839-4680 h x ng/mL). The half-life of ACP-103 was approximately 55 hours, with a t(max) at 6 hours. ACP-103 was well tolerated at single doses up to and including 300 mg and multiple doses up to 100 mg once daily for 14 days.
authors.affiliation: ACADIA Pharmaceuticals Inc, San Diego, California, USA. kvanover@intracellulartherapies.com
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Vanover
authors.forename: Doris
authors.initials: D
authors.lastname: Robbins-Weilert
authors.forename: Darren G
authors.initials: DG
authors.lastname: Wilbraham
authors.forename: Timothy G K
authors.initials: TG
authors.lastname: Mant
authors.forename: Daniel P
authors.initials: DP
authors.lastname: van Kammen
authors.forename: Robert E
authors.initials: RE
authors.lastname: Davis
authors.forename: David M
authors.initials: DM
authors.lastname: Weiner
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D058826:Serotonin 5-HT2 Receptor Agonists; D014508:Urea / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D010880:Piperidines; D058826:Serotonin 5-HT2 Receptor Agonists; D014508:Urea; C510793:pimavanserin