| Disease | 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 AN DNORGALANTAMINE WERE DETERMINED IN PLASMA AN DURINE 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 8MG), AND THERE WAS ANAPPROXIMATE DOSE PROPORTIONALITY OF
GALANTAMINE PHARMACOKINETIC PARAMETERS IN BOTH CAUCASIAN AND JAPANESE ETHNIC GROUPS. THE MEAN ((DL)-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) IN JAPANESE: CAUCASIAN SUBJECTS WITH 4 AND 8 MG DOSES WERE 103% (90% CONFIDENCE INTERVAL [CI]=92-116) AND 107% (90% CI=94-121], RESPECTIVELY. RATIOS FOR MAXIMUM PLASMA CONCENTRATION
(C-MAX) VALUES 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. |