Bypassing the first-pass effect for the therapeutic use of cannabinoids.
An oral formulation of delta-9-tetrahydrocannabinol (THC) in sesame oil (Marinol) is at present used for the management of chemotherapy-related nausea and emesis. However, due partly to poor bioavailability, its efficacy is variable. To circumvent possible metabolism in the gut and a first-pass effect by the liver, a suppository formulation of THC hemisuccinate ester was prepared. Administration of the suppository containing 11.8 mg of the hemisuccinate ester (equivalent to 9 mg THC) to three adult females (two of whom had previously exhibited low plasma drug levels following a 10-mg dose of the oral formulation) led to a marked and sustained elevation of plasma drug levels. Areas under the curves for plasma THC were more than 30-fold higher than after oral dosing. The suppository was well tolerated. The higher and more sustained plasma drug level achieved with this new formulation should enhance its antiemetic efficacy.
Monell Chemical Senses Center, Philadelphia, PA 19104-3308.
R D
RD
Mattes
L M
LM
Shaw
J
J
Edling-Owens
K
K
Engelman
M A
MA
Elsohly
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D013759:Dronabinol / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D013488:Suppositories
D013488:Suppositories; D013759:Dronabinol