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- Medical English LInking keywords finder for the PubMed Zipped Archive (ELIZA) -

return kwic search for demonstrated out of >500 occurrences
286534 occurrences (No.87 in the rank) during 5 years in the PubMed. [no cache] 500 found
2) Sensitivity analysis demonstrated that 11-OH-THC but not THC exposure was sensitive to alterations in hepatic intrinsic clearance of the respective compound.
--- ABSTRACT ---
PMID:33952608 DOI:10.1124/dmd.120.000322
2021 Drug metabolism and disposition: the biological fate of chemicals
* Development and Verification of a Linked Δ 9-THC/11-OH-THC Physiologically Based Pharmacokinetic Model in Healthy, Nonpregnant Population and Extrapolation to Pregnant Women.
- Conducting clinical trials to understand the exposure risk/benefit relationship of cannabis use is not always feasible. Alternatively, physiologically based pharmacokinetic (PBPK) models can be used to predict exposure of the psychoactive cannabinoid (-)-Δ9-tetrahydrocannabinol (THC) and its active metabolite 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC). Here, we first extrapolated in vitro mechanistic pharmacokinetic information previously quantified to build a linked THC/11-OH-THC PBPK model and verified the model with observed data after intravenous and inhalation administration of THC in a healthy, nonpregnant population. The in vitro to in vivo extrapolation of both THC and 11-OH-THC disposition was successful. The inhalation bioavailability (Finh) of THC after inhalation was higher in chronic versus casual cannabis users (Finh = 0.35 and 0.19, respectively). Sensitivity analysis demonstrated that 11-OH-THC but not THC exposure was sensitive to alterations in hepatic intrinsic clearance of the respective compound. Next, we extrapolated the linked THC/11-OH-THC PBPK model to pregnant women. Simulations showed that THC plasma area under the curve (AUC) does not change during pregnancy, but 11-OH-THC plasma AUC decreases by up to 41%. Using a maternal-fetal PBPK model, maternal and fetal THC serum concentrations were simulated and compared with the observed THC serum concentrations in pregnant women at term. To recapitulate the observed THC fetal serum concentrations, active placental efflux of THC needed to be invoked. In conclusion, we built and verified a linked THC/11-OH-THC PBPK model in healthy nonpregnant population and demonstrated how this mechanistic physiologic and pharmacokinetic platform can be extrapolated to a special population, such as pregnant women. SIGNIFICANCE STATEMENT: Although the pharmacokinetics of cannabinoids have been extensively studied clinically, limited mechanistic pharmacokinetic models exist. Here, we developed and verified a physiologically based pharmacokinetic (PBPK) model for (-)-Δ9-tetrahydrocannabinol (THC) and its active metabolite, 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC). The PBPK model was verified in healthy, nonpregnant population after intravenous and inhalation administration of THC, and then extrapolated to pregnant women. The THC/11-OH-THC PBPK model can be used to predict exposure in special populations, predict drug-drug interactions, or impact of genetic polymorphism.
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[frequency of next (right) word to demonstrated]
(1)169 that (11)5 good (21)3 that, (31)2 leadership
(2)48 a (12)5 using (22)2 altered (32)2 on
(3)34 the (13)5 with (23)2 benefits (33)2 positive
(4)18 in (14)4 comparable (24)2 decreases (34)2 potential
(5)17 to (15)4 for (25)2 elevated (35)2 robustness
(6)16 by (16)4 how (26)2 evidence (36)2 significantly
(7)9 an (17)4 its (27)2 greater (37)2 similar
(8)8 significant (18)3 improved (28)2 higher (38)2 statistically
(9)7 *null* (19)3 no (29)2 highly (39)2 successful
(10)7 efficacy (20)3 several (30)2 increased (40)2 survival

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--- WordNet output for demonstrated --- Overview of verb demonstrate The verb demonstrate has 4 senses (first 4 from tagged texts) 1. (24) show, demo, exhibit, present, demonstrate -- (give an exhibition of to an interested audience; "She shows her dogs frequently"; "We will demo the new software in Washington") 2. (22) prove, demonstrate, establish, show, shew -- (establish the validity of something, as by an example, explanation or experiment; "The experiment demonstrated the instability of the compound"; "The mathematician showed the validity of the conjecture") 3. (2) attest, certify, manifest, demonstrate, evidence -- (provide evidence for; stand as proof of; show by one's behavior, attitude, or external attributes; "His high fever attested to his illness"; "The buildings in Rome manifest a high level of architectural sophistication"; "This decision demonstrates his sense of fairness") 4. (1) demonstrate, march -- (march in protest; take part in a demonstration; "Thousands demonstrated against globalization during the meeting of the most powerful economic nations in Seattle") Overview of adj demonstrated The adj demonstrated has 1 sense (first 1 from tagged texts) 1. (1) demonstrated -- (having been demonstrated or verified beyond doubt) --- WordNet end ---