title: Galantamine pharmacokinetics, safety, and tolerability profiles are similar in healthy Caucasian and Japanese subjects.
abstract: The aim of this study was to compare the pharmacokinetics of galantamine in healthy Japanese and Caucasian subjects and assess the safety and tolerability of galantamine in both ethnic groups. Parallel groups of healthy Japanese (n = 13; 6 males and 7 females)and Caucasian (n = 12; 6 males and 6 females) subjects matched for weight and age received single oral doses of galantamine 4 mg, or galantamine 8 mg, or placebo in a double-blind, three-way crossover trial according to a randomized dosing schedule. Concentrations of galantamine and norgalantamine were determined in plasma and urine samples taken up to 48 and 24 hours after dosing, respectively. Safety and tolerability were monitored throughout the trial by recording adverse events, laboratory tests, and cardiovascular parameters. The mean plasma concentration-time profiles of galantamine were very similar after single doses of galantamine (4 and 8 mg), and there was an approximate dose proportionality of galantamine pharmacokinetic parameters in both Caucasian and Japanese ethnic groups. The mean (+/- SD) pharmacokinetic parameters in the two ethnic groups did not show any clinically relevant differences. The ratios for the area under the plasma-concentration curve from time zero to infinity (AUC)0-infinity) in Japanese:Caucasian subjects with 4 and 8 mg doses were 103% (90% confidence interval [CII = 92-116) and 107% (90% CI = 94-121), respectively. Ratios for maximum plasma concentration (Cmax) values were 107% (90% CI= 90-127) and 108% (90% CI= 95-123), respectively. These ratios and associated 90% CIs were within the 80% to 125% range limit of bioequivalence. Analysis of variance (ANOVA) showed that these ratio values demonstrated no statistically significant difference between the two ethnic groups. There was no overt difference in the adverse event profile in Japanese subjects compared with Caucasian subjects. There were no serious adverse events, and no subjects discontinued from the study because of adverse events. No consistent or clinically relevant pattern of blood chemistry, hematology, or cardiovascular changes was seen. These results suggest that the pharmacokinetic profiles of galantamine after single-dose administration are not statistically significantly different between Caucasian and Japanese groups. Galantamine was well tolerated. The safety and tolerability of galantamine were very similar in the two ethnic groups.
authors.affiliation: Global Clinical Pharmacokinetics and Clinical Pharmacology, Janssen Research Foundation, Titusville, New Jersey 08560-0200, USA.
authors.forename: Qinying
authors.initials: Q
authors.lastname: Zhao
authors.forename: Martin
authors.initials: M
authors.lastname: Brett
authors.forename: Nancy
authors.initials: N
authors.lastname: Van Osselaer
authors.forename: Fenglei
authors.initials: F
authors.lastname: Huang
authors.forename: Alain
authors.initials: A
authors.lastname: Raoult
authors.forename: Achiel
authors.initials: A
authors.lastname: Van Peer
authors.forename: Tom
authors.initials: T
authors.lastname: Verhaeghe
authors.forename: Rita
authors.initials: R
authors.lastname: Hust
mesh_terms: D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D005702:Galantamine / Q000009:adverse effects* / Q000493:pharmacokinetics*; D005838:Genotype; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D011110:Polymorphism, Genetic; D044465:White People
chemical_list: D005702:Galantamine; D019389:Cytochrome P-450 CYP2D6