Distribution studies of [ 14C]delta-9-tetrahydrocannabinol in mice: Effect of vehicle, route of administration, and duration of treatment

Abstract

The vehicle, route of administration, and duration of treatment affect the absorption, distribution, and excretion of delta-9-tetrahydrocannabinol (THC) in mice. [ 14C]THC [5 mg (20 μCi)/kg] was prepared in 10% Tween 80 and saline (TW) in 5% bovine serum albumin in water (BSA), in 10% propylene glycol−1% Tween 80 and saline (PPG) or in corn oil (COL). 14C concentration was measured in plasma, liver, brain, lung, and fat tissues. Total radioactivity in all tissues was lowest after po or sc administration, higher after ip, and highest after iv injection. After iv bolus injection, the 14C plasma concentration declined in a biphasic manner. Liver contained and retained the largest amount of 14C. Brain contained significantly less 14C than other tissues. Higher 14C plasma concentrations were seen at 1 hr after THC iv injection in PPG than with TW and BSA. BSA produced lower values than did PPG and TW. However, the 14C lung concentration was four times higher with BSA than that in PPG and TW. There were no significant differences in 14C brain concentrations 4 hr after iv administration of THC in TW, BSA, or PPG. However, TW produced significantly higher 14C brain values 1 hr after THC iv injection. Concentration of 14C in all tissues was significantly lower after THC ip or po administration in COL when compared to those found with TW. There was significantly more 14C excreted in the feces when compared to the amount measured in urine. Repeated iv administration of [ 14C]THC (5 days) produced high concentrations of 14C in liver, lung, and fat. Brain and plasma concentrations of 14C were lower following repeated administration.