Complement-Mediated Reactions to Diazepam With Cremophor as Solvent (Stesolid Mr)

Hüttel, M.; Olesen, Anne Vingaard; Stoffersen, Erik

doi:10.1093/bja/52.1.77

Cited by 74 publications

(18 citation statements)

References 8 publications

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“…In rodents, neurotoxicity, cardiotoxicity and nephrotoxicity due to IV ciclosporin dissolved in CrEL have been demonstrated [29–32] and, in a canine model, CrEL has been shown to reduce cardiac output and hepatic blood flow in a non-dose-dependent fashion [33]. The effects of CrEL include complement activation, histamine release and severe hypersensitivity reactions [14, 23, 25, 27]. …”

Section: Introductionmentioning

confidence: 99%

Bioequivalence and Tolerability Assessment of a Novel Intravenous Ciclosporin Lipid Emulsion Compared to Branded Ciclosporin in Cremophor® EL

Ehinger

Hansson

Sjövall

et al. 2012

Clinical Drug Investigation

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BackgroundCiclosporin is used as an immunosuppressant in current clinical practice but recent research implies novel indications for the drug, such as neuro- and cardioprotection. The intravenous formulation currently on the market, Sandimmune® Injection (Sandimmune®), uses Cremophor® EL as emulsifying excipient. Cremophor® EL is known to cause hypersensitivity reactions in some patients, ranging from skin reactions to potentially fatal anaphylactic shock.ObjectivesThe primary objective was to assess if CicloMulsion®, a Cremophor® EL-free lipid emulsion of ciclosporin for intravenous administration, is bioequivalent to Sandimmune®, and the secondary objective was to compare the tolerability profiles of the two preparations.MethodsThis was a single-centre, open-label, subject-blind, laboratory-blind, single-dose, randomized, two-treatment, two-period, two-sequence crossover study of the pharmacokinetics of two formulations of intravenous ciclosporin. Fifty-two healthy volunteer subjects were administered 5 mg/kg of each of the two formulations of ciclosporin as a 4-h intravenous infusion. The last blood sample was acquired 48 h after the end of the infusion. Bioequivalence assessments according to current guidelines were performed.ResultsThe geometric mean ratios for CicloMulsion®/Sandimmune® (90 % confidence interval [CI]) were 0.90 (0.88, 0.92) for AUC0–last (area under the blood concentration–time curve from time zero to time of last measurable concentration) and 0.95 (0.92, 0.97) for Cmax (maximum blood concentration). For all additional variables analysed, the 90 % CIs were also within the accepted bioequivalence range of 0.80–1.25. One anaphylactoid and one anaphylactic reaction, both classified as serious adverse events, were reported after treatment with Sandimmune®. No serious adverse events were recorded after treatment with CicloMulsion®.ConclusionWe have assessed the pharmacokinetics and tolerability of a new Cremophor® EL-free lipid emulsion of ciclosporin, CicloMulsion®, compared to Sandimmune®. The proportion of adverse events was significantly higher for the Cremophor® EL-based product Sandimmune®. We conclude that CicloMulsion® is bioequivalent to Sandimmune® and exhibits fewer adverse reactions.

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Section: Introductionmentioning

confidence: 99%

Bioequivalence and Tolerability Assessment of a Novel Intravenous Ciclosporin Lipid Emulsion Compared to Branded Ciclosporin in Cremophor® EL

Ehinger

Hansson

Sjövall

et al. 2012

Clinical Drug Investigation

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“…However, Tweens are known to be toxic, although less than Tritons [16]. Cremophor EL, which is used to solubilise various drugs like anaesthetics, photosensitizers, immunosuppressive agents, sedatives, anticancer and antitumor drugs, is reported to have side effects like severe anaphylactic hypersensitivity reactions, abnormal lipoprotein patterns, hyperlipidaemia and peripheral neuropathy [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Interaction between Zwitterionic Surfactants and Amphiphilic Drug: A Tensiometric Study

Ansari

Noori

Naqvi³

et al. 2013

Zeitschrift Für Physikalische Chemie

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Amitriptyline Hydrochloride / Zwitterionic Gemini Surfactants / Surface Tension / Mixed MicellesThe physicochemical properties, viz, critical micelle concentration (cmc), surface excess concentration (Γ max ), minimum area per head group ( A min ) of zwitterionic surfactants (designated as n(−)-2-m(+); n = 8, 10, 12 and m = 12, 14, 16) and their mixtures with amphiphilic antidepressant drug amitriptyline hydrochloride (AMT) were determined by using surface tension measurements. The cmc and ideal cmc (cmc id ) values along with interaction parameters, β m and β σ (calculated using Rubingh's and Rosen's models), suggest attractive interactions among the components. The Krafft temperature measurements also indicate strong attractive interactions. Γ max (or A min ) increases (or decreases) with the addition of gemini surfactant; the values being closer to that of the drug. These values and micellar mole fraction (X m 1 -calculated from Rubingh's model and X Moto 1 -calculated from Motomura's model) indicate larger contribution of gemini surfactants in mixed micelles and smaller contribution at air/solution interface (as mole fraction values at interface, X σ 1 , are slightly smaller than X m 1 ). The standard Gibbs energy of micellization (ΔG • mic ) and adsorption (ΔG • ad ) as well as excess energy of mixing (ΔG m ex ) are all negative. All these results suggest higher stability of the mixed systems. UV absorbance results also suggest that the mixed micelles are stable for several days.

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“…the highest cell mortality, was observed at the highest concentration of DTX after treatment for the longest time, which proved the controlled release of DTX from the NPs. This new DTX formulation of the multilayer NPs in the aqueous medium may minimize the adverse effects of the current free DTX formulation containing ethanol, such as anaphylaxis and severe hypersensitivity [22][23][24]. If the multilayer NPs is accumulated at the tumor site, enhanced antitumor efficacy is expected with reduced adverse effects [25].…”

Section: Physicochemical Properties Of the Multilayer Npsmentioning

confidence: 99%

The multilayer nanoparticles formed by layer by layer approach for cancer-targeting therapy

Lee

Kim

et al. 2013

Journal of Controlled Release

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Complement-Mediated Reactions to Diazepam With Cremophor as Solvent (Stesolid Mr)

Cited by 74 publications

References 8 publications

Bioequivalence and Tolerability Assessment of a Novel Intravenous Ciclosporin Lipid Emulsion Compared to Branded Ciclosporin in Cremophor® EL

Bioequivalence and Tolerability Assessment of a Novel Intravenous Ciclosporin Lipid Emulsion Compared to Branded Ciclosporin in Cremophor® EL

Interaction between Zwitterionic Surfactants and Amphiphilic Drug: A Tensiometric Study

The multilayer nanoparticles formed by layer by layer approach for cancer-targeting therapy

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