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  • 1
    ISSN: 1432-1041
    Schlagwort(e): Key words Grapefruit juice ; Triazolam ; Interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Objective: Grapefruit juice inhibits CYP3A4-mediated metabolism of several drugs during first pass. In this study, the effect of grapefruit juice dose on the extent of grapefruit juice–triazolam interaction was investigated. Methods: In a randomised, four-phase, crossover study, 12 healthy volunteers received 0.25 mg triazolam with water, with 200 ml normal-strength or double-strength grapefruit juice or, on the third day of multiple-dose [three times daily (t.i.d.)] administration of double-strength grapefruit juice. Timed blood samples were collected up to 23 h after dosing, and the effects of triazolam were measured with four psychomotor tests up to 10 h after dosing. Results: The area under the plasma triazolam concentration–time curve (AUC0–∞) was increased by 53% (P 〈 0.01), 49% (P 〈 0.01) and 143% (P 〈 0.001) by a single dose of normal-strength, a single dose of double-strength and multiple-dose administration of double-strength grapefruit juice, respectively. The peak plasma concentration (Cmax) of triazolam was increased by about 40% by a single dose of normal-strength grapefruit juice (P 〈 0.01) and multiple-dose grapefruit juice (P 〈 0.01) and by 25% by a single dose of double-strength grapefruit juice (P 〈 0.05). The elimination half-life (t 1/2) of triazolam was prolonged by 54% during the multiple-dose grapefruit juice phase (P 〈 0.001). A significant increase in the pharmacodynamic effects of triazolam was seen during the multiple-dose grapefruit juice phase in the digit symbol substitution test (DSST, P 〈 0.05), in subjective overall drug effect (P 〈 0.05) and in subjective drowsiness (P 〈 0.05). Conclusions: Even one glass of grapefruit juice increases plasma triazolam concentrations, but repeated consumption of grapefruit juice produces a significantly greater increase in triazolam concentrations than one glass of juice. Thet 1/2 of triazolam is prolonged by repeated consumption of grapefruit juice, probably due to inhibition of hepatic CYP3A4 activity.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Publikationsdatum: 2021-05-17
    Beschreibung: At least two transient events of extreme global warming occurred superimposed on the long-term latest Paleocene and early Eocene warming trend in the Paleocene-Eocene thermal maximum (PETM) (or ETM1 ~55.5 Ma) and the Elmo (or ETM2 ~53.6 Ma). Other than warmth, the best known PETM is characterized by (1) significant injection of 13C-depleted carbon into the ocean-atmosphere system, (2) deep-sea carbonate dissolution, (3) strong biotic responses, and (4) perturbations of the hydrological cycle. Documentation of the other documented and suspected "hyperthermals" is, as yet, insufficient to assess whether they are similar in nature to the PETM. Here we present and discuss biomagnetostratigraphic data and geochemical records across two lower Eocene successions deposited on a continental margin of the western Tethys: the Farra and Possagno sections in the Venetian pre-Alps. We recognize four negative carbon isotope excursions within chron C24. Three of these shifts correlate to known or suspected hyperthermals: the PETM, the Eocene thermal maximum 2 (~53.6 Ma), and the informally named "X event" (~52.5 Ma). The fourth excursion lies within a reverse subchron and occurred between the latter two. In the Farra section, the X event is marked by a ~0.6% negative carbon isotope excursion and carbonate dissolution. Furthermore, the event exhibits responses among calcareous nannofossils, planktic foraminifera, and dinoflagellates that are similar to, though less intense than, those observed across the PETM. Sedimentological and quantitative micropaleontological data from the Farra section also suggest increased weathering and runoff as well as sea surface eutrophication during this event.
    Beschreibung: Published
    Beschreibung: PA2209
    Beschreibung: 2.2. Laboratorio di paleomagnetismo
    Beschreibung: JCR Journal
    Beschreibung: reserved
    Schlagwort(e): Paleoclimate ; Hyperthermal events ; Early Eocene ; Bio-magnetostratigraphy ; Geochemistry ; 04. Solid Earth::04.04. Geology::04.04.10. Stratigraphy ; 04. Solid Earth::04.05. Geomagnetism::04.05.06. Paleomagnetism ; 04. Solid Earth::04.05. Geomagnetism::04.05.09. Environmental magnetism
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
    Standort Signatur Erwartet Verfügbarkeit
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