Tags

Type your tag names separated by a space and hit enter

Metabolism, disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women.
Clin Pharmacol Ther. 1983 Sep; 34(3):352-63.CP

Abstract

A comparative study was done in women and men of the effects of delta 9-tetrahydrocannabinol (delta 9-THC), intravenously or orally, on dynamic activity, metabolism, excretion, and kinetics. In general no differences between the two sexes were observed. delta 9-THC is converted by microsomal hydroxylation to 11-hydroxy-delta 9-THC (11-OH-delta 9-THC), which is both a key intermediate for further metabolism to 11-nor-delta 9-THC-9-carboxylic acid (11-nor-acid) by liver alcohol-dehydrogenase enzymes and a potent psychoactive metabolite. Major differences in the ratio of the concentration of 11-OH-delta 9-THC to that of delta 9-THC in plasma were found after intravenous dosing (ratio 1:10 to 20) compared with oral administration (ratio 0.5 to 1:1). The final metabolic products are the 11-nor-acids and the related, more polar acids. Urinary excretion of delta 9-THC is restricted to acidic nonconjugated and conjugated metabolites. After 72 hr mean cumulative urinary excretion, noted for both routes and for both sexes, ranged from 13% to 17% of the total dose. After 72 hr the cumulative fecal excretion for both sexes after intravenous administration ranged from 25% to 30%; after oral administration the range was 48% to 53%. Metabolites were found in the feces in large concentration in the nonconjugated form; concentrations of 11-OH-delta 9-THC were particularly noteworthy. Kinetics of delta 9-THC and metabolites were much the same for female and male subjects. For delta 9-THC, terminal-phase t1/2s for both sexes, irrespective of the route, ranged from 25 to 36 hr. A comparison of the results for AUC/dose (delta 9-THC) after oral dosing with comparable data from intravenous administration indicated bioavailability of the order of 10% to 20% for both sexes. After intravenous delta 9-THC, large apparent volumes of distribution were noted (about 10 l/kg for both sexes).

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

6309462

Citation

Wall, M E., et al. "Metabolism, Disposition, and Kinetics of Delta-9-tetrahydrocannabinol in Men and Women." Clinical Pharmacology and Therapeutics, vol. 34, no. 3, 1983, pp. 352-63.
Wall ME, Sadler BM, Brine D, et al. Metabolism, disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women. Clin Pharmacol Ther. 1983;34(3):352-63.
Wall, M. E., Sadler, B. M., Brine, D., Taylor, H., & Perez-Reyes, M. (1983). Metabolism, disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women. Clinical Pharmacology and Therapeutics, 34(3), 352-63.
Wall ME, et al. Metabolism, Disposition, and Kinetics of Delta-9-tetrahydrocannabinol in Men and Women. Clin Pharmacol Ther. 1983;34(3):352-63. PubMed PMID: 6309462.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metabolism, disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women. AU - Wall,M E, AU - Sadler,B M, AU - Brine,D, AU - Taylor,H, AU - Perez-Reyes,M, PY - 1983/9/1/pubmed PY - 1983/9/1/medline PY - 1983/9/1/entrez SP - 352 EP - 63 JF - Clinical pharmacology and therapeutics JO - Clin Pharmacol Ther VL - 34 IS - 3 N2 - A comparative study was done in women and men of the effects of delta 9-tetrahydrocannabinol (delta 9-THC), intravenously or orally, on dynamic activity, metabolism, excretion, and kinetics. In general no differences between the two sexes were observed. delta 9-THC is converted by microsomal hydroxylation to 11-hydroxy-delta 9-THC (11-OH-delta 9-THC), which is both a key intermediate for further metabolism to 11-nor-delta 9-THC-9-carboxylic acid (11-nor-acid) by liver alcohol-dehydrogenase enzymes and a potent psychoactive metabolite. Major differences in the ratio of the concentration of 11-OH-delta 9-THC to that of delta 9-THC in plasma were found after intravenous dosing (ratio 1:10 to 20) compared with oral administration (ratio 0.5 to 1:1). The final metabolic products are the 11-nor-acids and the related, more polar acids. Urinary excretion of delta 9-THC is restricted to acidic nonconjugated and conjugated metabolites. After 72 hr mean cumulative urinary excretion, noted for both routes and for both sexes, ranged from 13% to 17% of the total dose. After 72 hr the cumulative fecal excretion for both sexes after intravenous administration ranged from 25% to 30%; after oral administration the range was 48% to 53%. Metabolites were found in the feces in large concentration in the nonconjugated form; concentrations of 11-OH-delta 9-THC were particularly noteworthy. Kinetics of delta 9-THC and metabolites were much the same for female and male subjects. For delta 9-THC, terminal-phase t1/2s for both sexes, irrespective of the route, ranged from 25 to 36 hr. A comparison of the results for AUC/dose (delta 9-THC) after oral dosing with comparable data from intravenous administration indicated bioavailability of the order of 10% to 20% for both sexes. After intravenous delta 9-THC, large apparent volumes of distribution were noted (about 10 l/kg for both sexes). SN - 0009-9236 UR - https://www.unboundmedicine.com/medline/citation/6309462/Metabolism_disposition_and_kinetics_of_delta_9_tetrahydrocannabinol_in_men_and_women_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0009-9236&date=1983&volume=34&issue=3&spage=352 DB - PRIME DP - Unbound Medicine ER -