The effects of cremophor EL in the anaesthetized dog

Gaudy, J.H.; Sicard, Jean-François; Lhoste, F; Boitier, J.F.

doi:10.1007/bf03015328

Cited by 32 publications

(10 citation statements)

References 29 publications

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“…The marmoset can be used for pharmacology as well as for toxicology studies. In addition, there are well-established classes of compounds where the marmoset may well offer an alternative species to the dog that shows hypersensitivity or idiosyncrasy (Smith et al, 2001;Gaudy et al, 1987) (Table 6).…”

Section: Toxicologymentioning

confidence: 99%

Overview of the marmoset as a model in nonclinical development of pharmaceutical products

Orsi¹,

Rees²,

Andreini³

et al. 2011

Regulatory Toxicology and Pharmacology

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Callithrix jacchus (common marmoset) is one of the more primitive non-human primate species and is used widely in fundamental biology, pharmacology and toxicology studies. Marmosets breed well in captivity with good reproductive efficiencies and their sexual maturity is reached within 18 months of age allowing for rapid expansion of colonies and early availability of sexually mature animals permitting an earlier assessment of product candidates in the adult. Their relatively small size allows a reduction in material requirements leading to a reduction in development time and cost. Fewer animals are also required due to their ability to be used in both pharmacology and toxicology (nonclinical) studies. These factors, alongside a better understanding of their optimal nutrient and welfare requirements over recent years, facilitate the generation of a more cohesive and robust dataset. With the growth of biotechnology-derived pharmaceuticals, non-human primate use has, by necessity, also increased; nevertheless, there is also a growing public call for minimizing their use. Utilizing, the more primitive marmoset species may provide the optimal compromise and once the scientific rationale has been carefully considered and their use justified, there are several advantages to using the marmoset as a model in nonclinical development of pharmaceutical products.

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Section: Toxicologymentioning

confidence: 99%

Overview of the marmoset as a model in nonclinical development of pharmaceutical products

Orsi¹,

Rees²,

Andreini³

et al. 2011

Regulatory Toxicology and Pharmacology

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show abstract

“…[23][24][25] Cremophore EL emulsion has fewer lipophilic characteristics and easily crosses membranes and distributes among serum lipoproteins. Drug given with cremophore is also related to a slower clearance from the plasma and the parallel slower uptake in the liver.…”

Section: Introductionmentioning

confidence: 99%

“…[26][27][28] Thus, rapid absorption and longer residence were observed when using the cremophore formulation with various drugs. [24][25][26][27][28] The formulations of AM or AE with sesame oil (slow absorption) and cremophore (fast absorption) were also compared with their efficacy potency against Plasmodium berghei in mice. In addition, DQHS, an active metabolite of both AE and AM, is known to be extremely toxic in rats; 20 we also included it for comparison with AE and AM in this study.…”

Section: Introductionmentioning

confidence: 99%

Neurotoxicity and efficacy of arteether related to its exposure times and exposure levels in rodents.

Mog²,

Z³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. The neurotoxicity of ␤-arteether (AE) is related to drug accumulation in blood due to slow and prolonged absorption from the intramuscular injection sites. In this efficacy and toxicity study of AE, the traditional sesame oil vehicle was replaced with cremophore to decrease the accumulation and toxicity of AE. Dihydroartemisinin (DQHS), a more toxic and active metabolite of AE, was also analyzed. When administered at a daily dosage of 25 mg/kg for seven days, blood accumulation of AE with sesame oil (AESO) was used had a 7.5-fold higher area under the curve (AUC) (on last versus first day dosing), while AE with cremophore (AECM) had only a 1.8-fold higher AUC. Although the accumulation of AECM was greatly reduced, its total exposure level (46.29 g и h/ml) was 2.7-fold higher than with AESO (16.92 gиh/ml) due to a higher bioavailability of AECM (74.5%) compared with AESO (20.3%). Total exposure time (calculated at over the minimal detected neurotoxicity level of 41.32 ng/ml) of AECM was 103 hours during the whole treatment period (192 hours), which was more than one-third (37%) less than with AESO (162 hours). Similar pharmacokinetic results were also shown with the active metabolite, DQHS. Anorexia and gastrointestinal toxicity with AESO were significantly more severe than with AECM (P < 0.001). Histopathologic examination of the brain demonstrated neurotoxic changes; the AESO rat group was significantly more severe than the AECM rat group. The brain injury scores with AECM were mild to moderate (2.3-3.0), and with AESO they were moderate to severe (3.0-4.7) on day 7 and day 10, respectively. In addition, the results of a 50% cure dose (CD 50 ) against Plasmodium berghei in mice were 34.1 mg/kg for AESO and 14.2 mg/kg for AECM, indicating a significant higher efficacy was found in the AECM animals. Toxicity and efficacy of DQHS were also dependent on its exposure time and level, which was the same as its parent drug (AE). In conclusion, following the seven-day treatment in rats, AE and DQHS exposure time and level varied based on the vehicle used. The extension of drug exposure time and the low peak level of AE and DQHS were more associated with severe neurotoxicity and lower antimalarial efficacy, whereas the high level and short exposure time of AE and DQHS resulted in higher efficacy and milder toxicity.

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“…However, it has been observed that Cremophor EL induces hypersensitivity reactions in up to 9% of all human patients despite pretreatment . Hypersensitivity reactions also occur at a high rate in dogs, and the observations are similar to those in humans …”

Section: Introductionmentioning

confidence: 69%

Antitumour effects of Liporaxel (oral paclitaxel) for canine melanoma in a mouse xenograft model

Yang

Jin

Kim

et al. 2019

Vet Comparative Oncology

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Paclitaxel, a member of the taxane family, exhibits antitumour effects by targeting the microtubules in cancer cells. Recently, oral paclitaxel has been developed to overcome the side effects of intravenous paclitaxel administration in human patients. The objective of this study was to investigate the antitumour effects of oral paclitaxel in vitro and in vivo. Three weeks after inoculation, oral paclitaxel (25 and 50 mg/kg) or saline was administered every week for three consecutive weeks. To explore the underlying mechanism, tumour angiogenesis was examined by immunohistochemistry with an anti-CD31 antibody. Tumour cell apoptosis was detected by Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling assay, and cell cycle arrest was confirmed by western blot analysis. Oral paclitaxel treatment of canine melanoma

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The effects of cremophor EL in the anaesthetized dog

Cited by 32 publications

References 29 publications

Overview of the marmoset as a model in nonclinical development of pharmaceutical products

Overview of the marmoset as a model in nonclinical development of pharmaceutical products

Neurotoxicity and efficacy of arteether related to its exposure times and exposure levels in rodents.

Antitumour effects of Liporaxel (oral paclitaxel) for canine melanoma in a mouse xenograft model

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