| Disease | THE PHARMACOKINETICS AND TISSUE DISTRIBUTION OF TRITIUM-LABELLED BETA-SISTOSTEROL (BSS), AS WELL AS OF BSS EMBEDDED IN POLYETHYLENEGLYCOL (BSS-PEG), BSS IN MICROEMULSION (BSS-MICRO) AND BSS AS HEMISUCCINATE PRODRUG (BSS-HS), WERE STUDIED IN MALE
SPRAGUE-DAWLEY RATS FOLLOWING ORAL ADMINISTRATION OF BSS AND EACH DRUG PRODUCT EQUIVALENT TO 5 MG/KG BSS, RESPECTIVELY. TO CALCULATE THE ABSOLUTE ABSORPTION ESTIMATE, AN EQUAL AMOUNT OF BSS WAS ADMINISTERED ORALLY AND INTRAVENOUSLY AT THE SAME
DOSE. THE CONCENTRATION-TIME PROFILES FOR BOTH ROUTES OF ADMINISTRATION WERE BEST DESCRIBED BY A TWO-COMPARTMENT OPEN MODEL WITH A FAST DISTRIBUTION PHASE. THE MOST IMPORTANT PHARMACOKINETIC PARAMETERS, I.E. HALF-LIVES, AREA UNDER THE CURVES,
INITIAL BLOOD LEVELS FOR I.V. AND THE PEAK CONCENTRATIONS FOR P.O. ADMINISTRATION, RESPECTIVELY, WERE ESTIMATED FOR EACH DRUG PRODUCT. THE RESULTS SHOW THAT BSS-MICRO SIGNIFICANTLY INCREASES THE ABSORPTION. ON THE CONTRARY, PEG EMBEDMENT DOES
NOT INCREASE THE BLOOD LEVEL, AND DERIVATIZATION WITH SUCCINIC ACID SHOWS A LOWER AREA UNDER THE CURVE. TISSUE DISTRIBUTION WAS MONITORED AND THE HIGHEST LEVEL OF BSS WAS FOUND IN LIVER, LUNG AND SPLEEN WHEREAS BSS-MICRO GAVE A HIGHER AND BSS-
PEG AND BSS-HS GAVE A SOMEWHAT LOWER TISSUE DISTRIBUTION OF BSS. |