DEVELOPMENT OF A NEW DOSAGE FORM FOR LONG-TERM STUDIES OF ^9-THC

STUDIES IN THIS PROPOSAL WILL BE AIMED AT THE PREPARATION OFA SUPPOSITORY FORMULATION OF A PRO-DRUG OF DELTA-9-TETRA- HYDROCANNABINOL (^9-THC) AND STUDY THE BIOAVAILABILITY OF THC FROM THIS FORMULATION AS COMPARED TO I.V. ADMINISTRATIONOF BOTH THC AND ITS PRODRUG. BIOAVAILABILITY STUDIES WILL BE CONDUCTED IN MONKEYS, AND BLOOD SAMPLES WILL BE COLLECTEDAT 0, 15, 30, 60, 90, 120, 180, 240, AND 480 MINUTES AND THEN AT 24 HOURS FROM EACH TEST ANIMAL. ANALYSIS OF THE ^9-THC IN PLASMA WILL BE CARRIED OUT BOTH BY RIA AND GC/MS. INADDITION, PLASMA WILL BE ANALYZED BY GC/MS FOR 11-OH-^9-THC AND 11-NOR-^9-THC-9-COOH; THE LATTER COULD ALSO BE ASSAYED BY RIA. COMPARISON WILL BE MADE BETWEEN DATA OBTAINED FROM ^9-THC I.V. ANIMALS AND ANIMALS ADMINISTERED WITH THE NEW FORMULATION. THE AREA UNDER THE CURVE (CONCENTRATION OF ^9-THC VS TIME) CORRECTED FOR DOSE ADMINISTERED WILL BE TAKEN AS A DIRECT MEASURE OF THE BIOAVAILABILITY OF THC FROM THE NEW FORULATION. IN ADDITION, PRELIMINARY DATA WILL BE COLLECTED RELATIVE TO THE STABILITY OF THE FORMULATION. THE PROPOSED WORK COULD RESULT IN OVERCOMING THE ABSORPTION PROBLEMS ASSOCIATED WITH ORAL ADMINISTRATION OF THC AND POSSIBLE APPLICATION OF THIS CONCEPT TO OTHER HIGHLY LIPOPHYLIC DRUGS.