Refining procedures for the administration of substances

Morton, David B.; Jennings, Margaret; Buckwell, Anthony; Ewbank, Roger; Godfrey, Christopher J.; Holgate, B.; Inglis, Ian; James, Rolland; Page, C; Sharman, I. M.; Verschoyle, Richard D.; Westall, L.; Wilson, AB

doi:10.1258/0023677011911345

Cited by 190 publications

(69 citation statements)

References 25 publications

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“…However, the current availability of formulations of etomidate is very limited and, to the best of our knowledge, etomidate is only available in a concentration of 2 mg/mL. This means that injection volumes needed for at least one hour of sedation exceed the animal welfare guidelines . A recent paper showed that it was possible to measure unilateral BOLD responses upon a somatosensory stimulus repeatedly in the same mouse anesthesized with a novel ketamine/xylazine formulation .…”

Section: Discussionmentioning

confidence: 99%

Influence of different isoflurane anesthesia protocols on murine cerebral hemodynamics measured with pseudo‐continuous arterial spin labeling

et al. 2019

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Arterial spin labeling (ASL)‐MRI can noninvasively map cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), potential biomarkers of cognitive impairment and dementia. Mouse models of disease are frequently used in translational MRI studies, which are commonly performed under anesthesia. Understanding the influence of the specific anesthesia protocol used on the measured parameters is important for accurate interpretation of hemodynamic studies with mice. Isoflurane is a frequently used anesthetic with vasodilative properties. Here, the influence of three distinct isoflurane protocols was studied with pseudo‐continuous ASL in two different mouse strains. The first protocol was a free‐breathing set‐up with medium concentrations, the second a free‐breathing set‐up with low induction and maintenance concentrations, and the third a set‐up with medium concentrations and mechanical ventilation. A protocol with the vasoconstrictive anesthetic medetomidine was used as a comparison. As expected, medium isoflurane anesthesia resulted in significantly higher CBF and lower CVR values than medetomidine (median whole‐brain CBF of 157.7 vs 84.4 mL/100 g/min and CVR of 0.54 vs 51.7% in C57BL/6 J mice). The other two isoflurane protocols lowered the CBF and increased the CVR values compared with medium isoflurane anesthesia, without obvious differences between them (median whole‐brain CBF of 138.9 vs 131.7 mL/100 g/min and CVR of 10.0 vs 9.6%, in C57BL/6 J mice). Furthermore, CVR was shown to be dependent on baseline CBF, regardless of the anesthesia protocol used.

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Section: Discussionmentioning

confidence: 99%

Influence of different isoflurane anesthesia protocols on murine cerebral hemodynamics measured with pseudo‐continuous arterial spin labeling

et al. 2019

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“…The doses suggested in OECD TG 420 for investigating the toxicity of test chemicals are from 5 to 5000 mg/kg. We chose the concentration of 5 mg/Kg based on the maximum volume possible to administer to the animal by intraperitoneal pathway (10 mL/Kg) [ 23 ] and the maximum capacity of encapsulation of the chalcones into the nanoemulsion (0.5 mg/mL). A single dose was chosen to minimize the use of animals.…”

Section: Methodsmentioning

confidence: 99%

In vitro and in vivo Effects of Free and Chalcones-Loaded Nanoemulsions: Insights and Challenges in Targeted Cancer Chemotherapies

Winter

Pizzol

Locatelli

et al. 2014

IJERPH

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Several obstacles are encountered in conventional chemotherapy, such as drug toxicity and poor stability. Nanotechnology is envisioned as a strategy to overcome these effects and to improve anticancer therapy. Nanoemulsions comprise submicron emulsions composed of biocompatible lipids, and present a large surface area revealing interesting physical properties. Chalcones are flavonoid precursors, and have been studied as cytotoxic drugs for leukemia cells that induce cell death by different apoptosis pathways. In this study, we encapsulated chalcones in a nanoemulsion and compared their effect with the respective free compounds in leukemia and in non-tumoral cell lines, as well as in an in vivo model. Free and loaded-nanoemulsion chalcones induced a similar anti-leukemic effect. Free chalcones induced higher toxicity in VERO cells than chalcones-loaded nanoemulsions. Similar results were observed in vivo. Free chalcones induced a reduction in weight gain and liver injuries, evidenced by oxidative stress, as well as an inflammatory response. Considering the high toxicity and the side effects induced generally by all cancer chemotherapies, nanotechnology provides some options for improving patients’ life quality and/or increasing survival rates.

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“…This fact could be explained by that fact that in the intraperitoneal route, absorption occurs through the mesenteric vessels, draining to the portal vein, and thereby accessing the bloodstream in less time than by the oral route (Turner et al, 2011), making this a more rapid absorption route (Morton et al, 2001). Regarding the values obtained of k e , t 1/2 and the Cl/f, no significant difference was found that could be attributed to the administration route.…”

Section: Pharmacokineticmentioning

confidence: 97%

In vitro intestinal permeability studies, pharmacokinetics and tissue distribution of 6-methylcoumarin after oral and intraperitoneal administration in Wistar rats

Cárdenas

Kratz

Hernández

et al. 2017

Braz. J. Pharm. Sci.

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6-Methylcoumarin (6MC) is a semisynthetic coumarin with important in vitro and in vivo antiinflammatory activity. In order to continue the pre-clinical characterization of this molecule, in vitro intestinal permeability, plasma profile and tissue distribution after oral administration in rats were studied. The permeability of 6MC was evaluated by the Caco-2 cellular model in both the apical-basal (A-B) and basal-apical (B-A) directions. The pharmacokinetics and biodistribution were evaluated in rats after oral and intraperitoneal administration at doses of 200 mg/kg. Transport experiments with Caco-2 cells showed that 6MC presented high permeability at all concentrations evaluated. This finding suggested that 6MC could be transported across the gut wall by passive diffusion. The plasma concentration-time curve showed that the maximum concentration (Cmax) was 17.13 ± 2.90 µg/mL at maximum time (Tmax) of 30 min for the oral route and Cmax 26.18 ± 2.47 µg/mL at 6.0 min for the intraperitoneal administration, with elimination constant of (K e ) 0.0070 min -1 and a short life half time of (T

show abstract

Refining procedures for the administration of substances

Cited by 190 publications

References 25 publications

Influence of different isoflurane anesthesia protocols on murine cerebral hemodynamics measured with pseudo‐continuous arterial spin labeling

Influence of different isoflurane anesthesia protocols on murine cerebral hemodynamics measured with pseudo‐continuous arterial spin labeling

In vitro and in vivo Effects of Free and Chalcones-Loaded Nanoemulsions: Insights and Challenges in Targeted Cancer Chemotherapies

In vitro intestinal permeability studies, pharmacokinetics and tissue distribution of 6-methylcoumarin after oral and intraperitoneal administration in Wistar rats

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