title: Dose proportionality of moricizine after escalating multiple doses in healthy volunteers.
abstract: This study was designed to determine the dose linearity and proportionality of moricizine after multiple-dose administrations of 450 to 900 mg/day. The study design was an open-label, four-treatment, four-period sequentials escalating dose. Twelve subjects each received multiple doses of 150, 200, 250, and 300 mg of moricizine every 8 hours during 7 days of treatment. Blood samples for pharmacokinetic determinations were obtained on day 7 of each treatment period during an 8-hour time interval. Cmin determinations were also made on specific days of each treatment period. The AUC tau (area under the curve from time 0 to 8 hours), Cmax, and Cmin parameters were all normalized to the 250-mg (750 mg/day) dose. No statistically significant differences were seen in these parameters at the four treatment levels. It was concluded that moricizine follows first-order or linear pharmacokinetics after multiple dosing and exhibits dose proportional pharmacokinetics in the dosage-range studies. This range corresponds to the clinically useful dosage range.
authors.affiliation: Clinical Pharmacology Group, Du Pont Pharmaceuticals, Stine-Haskell Research, Newark, DE 19714.
authors.forename: I H
authors.initials: IH
authors.lastname: Benedek
authors.forename: D M
authors.initials: DM
authors.lastname: Garner
authors.forename: H J
authors.initials: HJ
authors.lastname: Pieniaszek
mesh_terms: D000284:Administration, Oral; D000328:Adult; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D016293:Moricizine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine
chemical_list: D016293:Moricizine