Linked Life Data

6256518

Source:http://linkedlifedata.com/resource/pubmed/id/6256518

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1981-3-27
pubmed:abstractText
The hypothesis was tested that the development of tolerance in man to the pharmacological effects of delta 9-tetrahydrocannabinol (THC) is due in part to changes in metabolism and disposition. Tolerance developed in six subjects following p.o. administration of 30 mg of THC every 4 hr for 10 to 12 days. Evaluation of THC pharmacokinetics was based on plasma levels of unchanged THC following i.v. administration of [14C] THC before and after the chronic p.o. THC. Development of tolerance was paralleled by pharmacokinetic changes: 1) average total metabolic clearance and the initial apparent volume of distribution increased from 605 to 977 ml/min and from 2.6 to 6.4 liters, respectively; 2) steady-state volume of distribution, averaging 684 liters, was unaltered; 3) the majority of model-dependent pharmacokinetic parameters as well as the time course of total metabolites in plasma were unchanged; 4) the percent dose excreted in urine decreased from 23.2 to 17.5%, but total elimination (urine plus feces) was not significantly changed; and 5) metabolites were rapidly formed (t 1/2 = 2.8-4.4 min), but slowly eliminated (t 1/2 = 49-53 hours) because of extensive protein binding. Renal clearance values of total metabolites were surprisingly low (maximum of 18-20 ml/min) and decreased with time (approximately 1 ml/min after 4-5 days), indicating the accumulation of highly bound metabolites. We conclude that such pharmacokinetic and metabolic changes cannot account for the development of tolerance to the cardiovascular, psychological and skin hypothermic effects of THC.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
215
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35-44
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1980
pubmed:articleTitle
Tolerance and disposition of tetrahydrocannabinol in man.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.