Histamine release in dogs by Cremophor El® and its derivatives: Oxethylated oleic acid is the most effective constituent

Lorenz, W.; Reimann, H. J.; Schmal, A.; Dormann, P.; Schwarz, Bernhard; Neugebauer, E.; Doenicke, Α.

doi:10.1007/bf01964882

Cited by 205 publications

(103 citation statements)

References 12 publications

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“…In the anaesthetized dog model, the hydrophilic components did not release histamine. Of the hydrophobic components (composed of 80 % derivatives of ricinoleic acid, 5 % derivatives of oleic acid), only the derivatives of oleic acid released histamine [11]. Further experimentation indicated that the derivatives of 12-hydroxystearic acid were the least dangerous in this test system [13].…”

Section: Discussionmentioning

confidence: 78%

See 1 more Smart Citation

Modulation of histamine release by fatty acids. A new in vitro model investigating adverse drug reactions in various species

Ennis

Lorenz

1985

Annales Françaises d'Anesthésie et de Réanimation

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: Histamine release caused by drugs and/or their solvents is a well known phenomenon. In this study, both in vivo (anaesthetized and conscious dogs) and in vitro (isolated rat peritoneal, human and guinea-pig lung mast cells) models were used. Cremophor E1 and six derivatives of 12-hydroxystearic acid were compared for their histamine releasing abilities. Although the three types of isolated mast cells responded similarly, histamine release being observed with DH (the diester of 12-hydroxystearic acid with polyethylene glycol), TN (12-hydroxystearic acid polymerized with ethylene oxide) and ME (the monoester of 12-hydroxystearlc acid esterified with polyethylene glycol), the anaesthetized dog exhibited elevated blood histamine levels and clinical symptoms after administration of all the solubilizing agents, except TN and ME. The reasons for this discrepancy are not known. The addition of the drugs (Althesin or propanidid) to their solubilizing agents caused histamine release, which was not observed with the solubilizing agent alone. This is the first demonstration of an in vitro model, which copies the clinical situation, i.e. solvent does nothing but the solvent plus drug combination causes histamine release and hence adverse reactions.RESUMe : La hb6ration d'histamine, due h des produits anesth6si-ques et/ou ~ leurs solvants, est un ph6nom6ne bien connu. Deux mod61es ont 6t6 utihs6s au cours de cette 6tude : l'un in vivo (chez le chlen anesth6si6 ou 6veill6), l'autre in vitro (sur des mastocytes xsol6s de p6ritoine de rat, de poumon humain ou de cobaye). Les capacit6s histaminolib6ratrices du cr6mophor E1 et de six d6riv6s de l'aclde 12-hydroxyst6arique ont 6t6 compar6es. Quoique les trois types de mastocytes isol6s aient r6agi de fa~on analogue, l'histaminolib6ration 6tant observ6e avec le DH (diester de l'acide 12-hydroxyst6afique + poly6thyl~ne glycol), le TN (acide 12-hydroxyst6arique polym6ns6 avec de l'oxyde d'6thyl6ne) et le ME (monoester de l'aclde 12-hydroxyst6arique est6rifi6 avec du poly6thyl6ne glycol), le chien anesth6si6 pr6sente un taux d'histamine 61ev6 et des sympt6mes chniques apr~s administration de tousles agents solvants, sauf le TN et le ME. Les raisons de cette dxff6rence ne sont pas connues. L'adjonction d'Alfat6sine ou de propanidide aux agents solvants entralne une histaminolib6-ration, qui n'6talt pas observ6e avec le solvant seul. Cette 6tude est le premier exemple d'un mod61e in vitro, copiant la situation clinique : le solvant n'entralne pas de r6action, mals l'adjoncnon de prodmt ~t ce dernier provoque une histaminolib6ration et donc des effets secondaires.Adverse reactions to drugs used during anaesthesia and surgery are common. Although reported incidences vary considerably, using data obtained from 23 carefully controlled clinical trials, the following incidences were obtained: all reactions 20-30 %, systemic reactions 1-5 % and life-threatening reactions 0.1-0.5 % [8]. In many cases, these reactions appear to be caused not by the drug itself but by the combination of...

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Section: Discussionmentioning

confidence: 78%

“…There has been much work published on the histamine releasing ability of cremophor and its derivatives using in vivo models [11][12][13]. Cremophor El, produced by the oxethylation of castor oil at elevated temperatures in an alkaline medium, is a mixture of hydrophilic and hydrophobic components [12].…”

Section: Discussionmentioning

confidence: 99%

Modulation of histamine release by fatty acids. A new in vitro model investigating adverse drug reactions in various species

Ennis

Lorenz

1985

Annales Françaises d'Anesthésie et de Réanimation

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“…Since paclitaxel injection contains the surfactant Cremophor-EL, which is reported to stimulate the release of histamine from mast cells, 19,20 histamine has been considered to be the predominant cause of HSRs associated with paclitaxel injection. 2,21 However, in the present study, there was no difference in the plasma histamine concentrations before and during paclitaxel infusion, thereby suggesting the lack of involvement of histamine in the pathogenesis of HSRs to paclitaxel.…”

Section: Discussionmentioning

confidence: 99%

Prophylactic effect of pemirolast, an antiallergic agent, against hypersensitivity reactions to paclitaxel in patients with ovarian cancer

Yahata

Saito

Sendo

et al. 2006

Intl Journal of Cancer

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We have previously shown that sensory nerve peptides contribute to the pathogenesis of pulmonary hypersensitivity reactions (HSRs) to paclitaxel in rats. Moreover, pemirolast, an antiallergic agent, reverses the HSRs to paclitaxel, although the mechanism is considered to result from the blockade of paclitaxel-induced release of sensory peptides, rather than the inhibition of histamine release. In the present study, we investigated the preventive effect of pemirolast against acute HSRs in a total of 84 patients who undertook postoperative paclitaxel plus carboplatin chemotherapy every 4 weeks for ovarian cancer. Patients were assigned to receive oral lactose (placebo) or pemirolast (10 mg), 2 hr before paclitaxel infusion. All patients received conventional premedication, including oral diphenhydramine, intravenous ranitidine and intravenous dexamethasone, 30 min before paclitaxel infusion. The HSRs that led to the discontinuance of paclitaxel infusion (grade 2) occurred in 5 of 42 patients in placebo group, whereas none of pemirolast-treated 42 patients showed any signs of HSRs. Plasma histamine concentrations were not changed after paclitaxel infusion in either group. Our present findings suggest that pemirolast is potentially useful for prophylaxis of paclitaxelinduced HSRs. In this respect, the use of pemirolast as premedication is expected to be beneficial to the safety management in patients who undergo chemotherapy containing paclitaxel. ' 2005 Wiley-Liss, Inc.Key words: paclitaxel; hypersensitivity reactions; pemirolast; histamine; ovarian cancer Paclitaxel (Taxol) is a widely used chemotherapeutic agent for several malignancies, including ovarian cancer, breast cancer, endometrial cancer, nonsmall-cell lung cancer and stomach cancer. However, the use of paclitaxel is sometimes limited due to the incidence of severe hypersensitivity reactions (HSRs). The HSRs to paclitaxel are characterized by flushing, chest discomfort, respiratory distress and pulmonary edema, 1-4 and the incidence is particularly high in patients with ovarian cancer who undertook postoperative chemotherapy containing paclitaxel. 5 To avoid the HSRs, premedication containing histamine H 1 and H 2 antagonists in combination with glucocorticoids is always prescribed, [6][7][8][9][10] although the preventive effect is by no means complete. However, there has been no direct evidence suggesting that the HSRs to paclitaxel are mediated by the release of histamine from mast cells or basophils. We have recently shown that paclitaxel causes pulmonary vascular hyperpermeability and edema and the decrease in arterial partial oxygen pressure in rats.11 The toxic effects of paclitaxel in rat lungs are attenuated by neurokinin NK 1 and NK 2 receptor antagonists, or chemical sensory denervation with repeated capsaicin treatment, but not by histamine H 1 or H 2 antagonists, thereby suggesting that the pulmonary adverse reactions induced by paclitaxel are mediated by sensory nerve peptides such as substance P and neurokinin A, but not by mast cell hista...

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“…Because paclitaxel is poorly soluble in water, the clinical formulation (e.g., Taxol®) contains Cremophor EL and ethanol. Cremophor EL can cause acute, severe anaphylactoid responses in humans (12,13), and a variety of alternative formulations have been developed, including microparticulate phospholipid-based (liposomal) formulations (L-pac) (14)(15)(16). In both animal models and humans, the toxicity of L-pac is significantly lower than that of Cre-pac (15,17,18), and therefore, analysis of PD data for L-pac was a motivating interest for this work.…”

Section: Pharmacokinetic Model For Paclitaxelmentioning

confidence: 99%

Comparison of Two Pharmacodynamic Transduction Models for the Analysis of Tumor Therapeutic Responses in Model Systems

Yang

Mager

Straubinger

2009

AAPS J

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Abstract. Semi-mechanistic pharmacodynamic (PD) models that capture tumor responses to anticancer agents with fidelity can provide valuable insights that could aid in the optimization of dosing regimens and the development of drug delivery strategies. This study evaluated the utility and potential interchangeability of two transduction-type PD models: a cell distribution model (CDM) and a signal distribution model (SDM). The evaluation was performed by simulating dense and sparse tumor response data with one model and analyzing it using the other. Performance was scored by visual inspection and precision of parameter estimation. Capture of tumor response data was also evaluated for a liposomal formulation of paclitaxel in the paclitaxel-resistant murine Colon-26 model. A suitable PK model was developed by simultaneous fitting of literature data for paclitaxel formulations in mice. Analysis of the simulated tumor response data revealed that the SDM was more flexible in describing delayed drug effects upon tumor volume progression. Dense and sparse data simulated using the CDM were fit very well by the SDM, but under some conditions, data simulated using the SDM were fitted poorly by the CDM. Although both models described the dose-dependent therapeutic responses of Colon-26 tumors, the fit by the SDM contained less bias. The CDM and SDM are both useful transduction models that recapitulate, with fidelity, delayed drug effects upon tumor growth. However, they are mechanistically distinct and not interchangeable. Both fit some types of tumor growth data well, but the SDM appeared more robust, particularly where experimental data are sparse.

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Histamine release in dogs by Cremophor El® and its derivatives: Oxethylated oleic acid is the most effective constituent

Cited by 205 publications

References 12 publications

Modulation of histamine release by fatty acids. A new in vitro model investigating adverse drug reactions in various species

Modulation of histamine release by fatty acids. A new in vitro model investigating adverse drug reactions in various species

Prophylactic effect of pemirolast, an antiallergic agent, against hypersensitivity reactions to paclitaxel in patients with ovarian cancer

Comparison of Two Pharmacodynamic Transduction Models for the Analysis of Tumor Therapeutic Responses in Model Systems

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