| Disease | GALANTAMINE OBTAINED IN HUMANS. THE PHARMACOKINETIC PROFILE OF GALANTAMINE AFTER REPEATED ORAL ADMINISTRATION IN RATS WAS MOST SIMILAR TO THE PROFILE OBTAINED AFTER REPEATED ADMINISTRATION OF 12 MG B.I.D. IN MAN.
APPROXIMATELY 75% OF GALANTAMINE EXPOSURE. GALANTAMINE PLASMA LEVELS AFTER SINGLE AND REPEATED ADMINISTRATION OF 10 MG/KG/DAY IN ALL SPECIES INVESTIGATED EXCEPT FEMALE RAT AND RABBIT WERE MUCH HIGHER THAN MEAN THERAPUETIC PLASMA LEVELS OF
GALANTAMINE OBTAINED AS A NATURAL EXTRACT OR FROM CHEMICAL SYNTHESIS. THE EXPOSURE TO THE ACTIVE METABOLITE NORGALANTAMINE IN PLASMA OF THE DIFFERENT ANIMAL SPECIES WAS LOW, EXCEPT IN THE DOG WHERE THE STEADY-STATE NORGALANTAMINE EXPOSURE WAS
LOWER IN FEMALES THAN IN MALES, WHEREAS IN MICE, FEMALES SHOWED HIGHER LEVELS THAN MALES. NO GENDER DIFFERENCES WERE OBSERVED IN DOGS. NO RELEVANT DIFFERENCES IN EXPOSURE TO GALANTAMINE WERE FOUND IN RATS AND DOGS UPON ORAL ADMINISTRATION OF
GAVAGE. ELIMINATION HALF-LIFE OF GALANTAMINE WAS RELATIVELY LARGE IN RAT AND DOG AND SMALLER IN MOUSE AND RABBIT. IN GENERAL, GALANTAMINE DISPLAYED DOSE-PROPORTIONAL TO SOMEWHAT MORE THAN DOSE-PROPORTIONAL KINETICS. IN RATS, PLASMA LEVELS WERE
REACHED WITHIN 2 H IN ALL SPECIES. ABSOLUTE ORAL BIOAVAILABILITY OF A GAVAGE DOSE WAS HIGH IN RAT (77%) AND DOG (78%). IN MICE AND RATS, THE BIOAVAILABILITY OF GALANTAMINE ADMINISTERED VIA THE FOOD WAS LOWER THAN GALANTAMINE ADMINISTERED BY
DOSES UP TO 32 MG/KG/DAY WERE ADMINISTERED TO FEMALE PREGNANT RABBITS. BEAGLE DOGS RECEIVED SINGLE I.V. AND SINGLE AND REPEATED ORAL ADMINISTRATION OF DOSES UP TO 8 MG/KG/DAY. GENERALLY, ORAL ABSORPTION WAS RAPID, WITH MAXIMAL PLASMA LEVELS
RATS RECEIVED SINGLE I.V. AND SINGLE AND REPEATED ORAL ADMINISTRATIONS OF VARIOUS DOSES, UP TO 160 MG/KG/DAY. IN MICE, ONLY REPEATED ORAL ADMINISTRATION OF GALANTAMINE WAS INVESTIGATED, UP TO 40 MG/KG/DAY. GALANTAMINE SINGLE AND REPEATED ORAL |