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• W2234783912 abstract "The time course of intravenously administered Δ 9 -tetrahydrocannabinol (Δ 9 -THC) in various species can be fitted by a sum of up to five exponentials, indicative of variable rates of permeation into and return from multiple body compartments. No dose dependent pharmacokinetics has been observed. The drug is rapidly and completely metabolized, concomitantly with its rapid distribution into, and sequestration by, tissues. Both bound and unbound Δ 9 -THC in the plasma are effectively cleared by the liver with a 50% hepatic efficiency referenced to total drug in plasma. The overall volume of distribution referenced to plasma-unbound drug is 50–100 × 10 3 liters. The terminal slow decay of Δ 9 -THC in the body with apparent half lives of up to 7 days is due to its slow release from these tissues. This terminal phase could not be significantly affected by any enzymic induction. Such a phenomenon implies a high accumulation in body tissues; the amount of Δ 9 -THC in the body would be 10-fold greater than from a single dose after 27 days of repetitive daily dosing. The slow elimination of metabolites is a consequence of the slow rate-determining return of Δ 9 -THC from deep compartments to the plasma. Intravenously administered metabolites are rapidly eliminated. In general by 5 days, 15–17% of the dose appears as metabolites in the urine and 40–45% is biliary excreted to appear in the feces. The studies in bile cannulated dogs show a 15% enterohepatic recirculation of biliary excreted metabolites. Available data is consistent with a similar pharmacokinetic pattern for the primary metabolite 11-hydroxy Δ 9 -tetrahydrocannabinol. The high non-saturable protein binding (97%) of Δ 9 -THC can be used to solubilize this highly insoluble material (0.77 mg/l in 0.15 M NaCl at 23°). Δ 9 -THC is rapidly degraded in acidic solutions and the kinetics have been completely determined." @default.
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• W2234783912 date "1979-01-01" @default.
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• W2234783912 title "PHARMACOKINETICS AND DISPOSITION OF Δ9-TETRAHYDROCANNABINOL AND ITS METABOLITES" @default.
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• W2234783912 doi "https://doi.org/10.1016/b978-0-08-023759-6.50014-7" @default.
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