title: Urinary pharmacokinetics of 11-nor-9-carboxy-delta9-tetrahydrocannabinol after controlled oral delta9-tetrahydrocannabinol administration.
abstract: Understanding the pharmacokinetics of orally administered cannabinoids is vitally important for optimizing therapeutic usage and to determine the impact of positive tests on drug detection programs. In this study, gas chromatography-mass spectrometry (limit of quantitation = 2.5 ng/mL) was used to monitor the excretion of total 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THCCOOH) in 4381 urine voids collected from seven participants throughout a controlled clinical study of multiple oral doses of THC. The National Institute on Drug Abuse Institutional Review Board approved the study and each participant provided informed consent. Seven participants received 0, 0.39, 0.47, 7.5, and 14.8 mg THC/day for five days in this double blind, placebo-controlled, randomized protocol conducted on a closed research ward. No significant differences (P </= 0.05) were observed in mean time of maximum excretion rate, mean maximum excretion rate, and mean terminal elimination half-life (t(1/2)) between the four THC doses, with ranges of 67.4 to 94.9 h, 0.9 to 16.3 micro g/h, and 44.2 to 64.0 h, respectively. Mean apparent elimination t(1/2) of 24.1 +/- 7.8 and 21.1 +/- 4.3 h for the 7.5 and 14.8 mg/day doses, respectively, were calculated from the excretion rate curve prior to the last urine sample with a THCCOOH concentration >/= 15 ng/mL. An average of only 2.9 +/- 1.6%, 2.5 +/- 2.7%, 1.5 +/- 1.4%, and 0.6 +/- 0.5% of the THC in the 0.39, 0.47, 7.5, and 14.8 mg/day doses, respectively, was excreted as THCCOOH in the urine over each 14-day dosing session. This study demonstrated that the terminal urinary elimination t(1/2) of THCCOOH following oral administration was approximately two to three days for doses ranging from 0.39 to 14.8 mg/d. These data also demonstrate that the apparent urinary elimination t(1/2) of THCCOOH prior to reaching a 15 ng/mL concentration is significantly shorter than the terminal urinary elimination t(1/2). These controlled drug administration data should assist in the interpretation of urine cannabinoid results and provide clinicians with valuable information for future pharmacological studies.
authors.affiliation: Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gustafson
authors.forename: Insook
authors.initials: I
authors.lastname: Kim
authors.forename: Peter R
authors.initials: PR
authors.lastname: Stout
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Klette
authors.forename: M P
authors.initials: MP
authors.lastname: George
authors.forename: Eric T
authors.initials: ET
authors.lastname: Moolchan
authors.forename: Barry
authors.initials: B
authors.lastname: Levine
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002188:Cannabis; D004304:Dosage Forms; D013759:Dronabinol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000652:urine*; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans
chemical_list: D018712:Analgesics, Non-Narcotic; D004304:Dosage Forms; C016780:11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid; D013759:Dronabinol