Pharmacokinetic and bioequivalence study of itopride HCl in healthy volunteers.
In the present study two different formulations containing 50 mg itopride HCl (N-[4-12-(dimethylamino)ethoxylbenzyl]-3,4-dimethoxybenzamide HCl, CAS 122898-67-3) were compared in 28 healthy male volunteers in order to compare the bioavailability and prove the bioequivalence. The study was performed in an open, single dose randomized, 2-sequence, crossover design in 28 healthy male volunteers with a one-week washout period. Blood samples for pharmacokinetic profiling were drawn at selected times during 24 h. The serum concentrations of itopride HCl were determined using a specific and sensitive HPLC method with fluorescence detection. The detection limit of itopride HCl was 5 ng/ml and no endogenous compounds were found to interfere with analysis. The mean AUC(0-4h), AUC(0 --> infinity), C(max), T(max) and T1/2 were 865.28 ng x h/ml, 873.04 ng x h/ml, 303.72 ng/ml, 0.75 h, and 2.95 h, respectively, for the test formulations, and 833.00 ng x h/ml, 830.97 ng x h/ml, 268.01 ng/ml, 0.78 h, and 2.83 h, respectively, for the reference formulation. Both primary target parameters AUC(0 --> infinity) and C(max) were log-transformed and tested parametrically by analysis of variance (ANOVA). 90% confidence intervals of AUC(0 --> infinity) and C(max) were 100.57%-109.56% and 105.46%-121.18%, respectively, and were in the range of acceptable limits of bioequivalence (80-125%). Based on these results, the two formulations of itopride HCl are considered to be bioequivalent.
Cho
Kyung-Jin
KJ
Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University, Daejeon, Korea.
Cho
Wonkyung
W
Cha
Kwang-Ho
KH
Park
Junsung
J
Kim
Min-Soo
MS
Kim
Jeong-Soo
JS
Hwang
Sung-Joo
SJ
D000932:Antiemetics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001549:Benzamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001593:Benzyl Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002138:Calibration; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D006801:Humans; D012015:Reference Standards; D012996:Solutions; D013050:Spectrometry, Fluorescence; D013607:Tablets; D013810:Therapeutic Equivalency
D000932:Antiemetics; D001549:Benzamides; D001593:Benzyl Compounds; D012996:Solutions; D013607:Tablets; C102254:itopride