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.
Mattes
R D
RD
Monell Chemical Senses Center, Philadelphia, PA 19104-3308.
Shaw
L M
LM
Edling-Owens
J
J
Engelman
K
K
Elsohly
M A
MA
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