Dose proportionality of moricizine after escalating multiple doses in healthy volunteers.
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.
Benedek
I H
IH
Clinical Pharmacology Group, Du Pont Pharmaceuticals, Stine-Haskell Research, Newark, DE 19714.
Garner
D M
DM
Pieniaszek
H J
HJ
D000284:Administration, Oral; D000328:Adult; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D016293:Moricizine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine
D016293:Moricizine