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Siddik ZH, Barnes RD, Dring LG, Smith RL, Williams RT. 
“The fate of lysergic acid di[14C]ethylamide ([14C]LSD) in the rat, guinea pig and rhesus monkey and of [14C]iso-LSD in rat”. 
Biochemical Pharmacology. 1979 Mar;28:3093-3101.
Abstract
The qualitative and quantitative aspects of the metabolism and elimination of [14C]LSD in the rat, guinea pig and rhesus monkey have been investigated. Rats given an i.p. dose ( 1 mg/kg) excreted 730f the 14C in the faeces, 16 0n the urine and 3.4 0n the expired air as 14CO2 in 96 hr. Guinea pigs similarly dosed, excreted 40 0n the farces, 28% (urine) and 18% (expired 14CO2) in 96 hr. Rhesus monkeys (0.15 mg/kg i.m.) eliminated 390f the 14C in the urine and 23 0n the faeces in 96 hr. Extensive binary excretion of [l4C]LSD occurred in both the rat and guinea pig. Bile duct-cannulated rats excreted 680f an i.v. dose (1.33 mg/kg) in the bile in 5 hr and the guinea pig 52 0n 6 hr. [14C]LSD is almost completely metabolized by all three species and little unchanged drug is excreted. The metabolites identified were 13- and 14-hydroxy-LSD and their glucuronic acid conjugates, 2-oxo-LSD. de-methyl LSD and a naphthostyril derivative. There occur, however important species differences in the nature and amounts of the various metabolites. In the rat and guinea pig the major metabolites were the glucuronic acid conjugates of 13- and 1 4-hydroxy-LSD which were found in both urine and bile. The guinea pig excreted significant amounts of 2-oxo-LSD in urine and bile, De-ethyl LSD was a minor urinary metabolite in both species. The metabolism of LSD appeared to be more complicated in the rhesus monkey. The urine contained at least nine metabolizes of which four were identified as follows: 13- and 14-hydroxy-LSD (as glucuronic acid conjugates) de-ethyl LSD and a naphthostyril derivative. Unlike the rat and guinea pig the glucuronic acid conjugates of 13- and 14-hydroxy-LSD were only present in small amounts. Of the remaining five unidentified metabolizes, three were major. The biliary metabolites of [14C]iso-LSD in the rat have been studied and been shown to be similar to those produced from [14C]LSD, namely 13- and 14-hydroxy-iso-LSD and their glucuronic acid conjugates and 2oxo-iso-LSD.
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