Paclitaxel Cremophor

Both drugs are highly lipid soluble and as such are prepared and administered in dilutants (paclitaxel in Cremophor EL and docetaxel in polysorbate 80). Both medications are normally administered with dexamethasone, H, and H2 antagonists as premedications to decrease the incidence of the acute hypersensitivity reaction (HSR) (dyspnea with bronchospasm, urticaria, and hypotension) that has been observed to occur... 

In terms of biodistribution, Zhang et al. (1997) were not able to demonstrate any difference between the biodistribution of paclitaxel loaded into MePEGQLLA micelles versus paclitaxel solubilized in Cremophor EL (a conventional surfactant). These two formulations also showed similar in vitro distribution between the lipoprotein and lipoprotein-deLcient fraction of plasma (Ramaswamy et al., 1997). As for other drug carriers, plasma half-life and uptake of polymeric micelles by the MPS depend on the molecular weight (Kwon et al., 1994) and density of the hydrophilic shell (Hagan et al., 1996). 

Liebmann, J., Cook, J., and Lipschultz, C. (1994). The in uence of Cremophor EL on the cell cycle effects of paclitaxel (Taxol) in human tumor cell line ancer Chemother. Pharmacol., 33, 331-339. 

Effect of paclitaxel-LCM and paclitaxel-cremophor on cell survival in vitro. (Taken from ref. 532.)... 

Fig. 13.10 This photomicrograph demonstrates the tumor morphology of Fischer 344 rats bearing 9L gliosarcomas treated with cremophor-LCM (A) and paclitaxel-LCM (B,C). Experimental animals received one i.v. injection of 240 pg/kg paclitaxel-LCM each day for 5 consecutive days starting 10 days after the tumor inoculation. Control animals received cremophor-LCM. Tumors from animals treated with paclitaxel-LCM show extensive cell death (B) and hemorrhage (C). (Taken from ref. 532.)...

Ciutaru D, Badea I, Lazar L, Nicolescu D, Tudose A. 2004. A HPLC validated assay of paclitaxel s related impurities in pharmaceutical forms containing Cremophor EL. J. Pharm. Biomed. Anal. 34 493-499. 

Drug-loaded nanoparticles were also evaluated for their safety and efficacy. Paclitaxel-encapsulated 6-O-CAPRO-p-CD nanospheres and nanocapsules were evaluated for their physical stability in a one-month period in aqueous dispersion form with repeated particle size and zeta potential measurements and AFM imaging to evaluate recrystallization in aqueous medium. Paclitaxel-loaded amphiphilic CD nanoparticles were found to be physically stable for a period of one month whereas recrystallization occurs within minutes when diluted for intravenous (IV) infusion [85], Finally, paclitaxel-loaded amphiphilic nanoparticles were demonstrated to show similar anticancer efficacy against MCF-7 cells when compared to paclitaxel solution in a cremophor vehicle [85],... 

EPIRUBICIN ANTICANCER AND IMMUNOMODULATING DRUGS-PACLITAXEL t plasma concentrations of epirubicin (t AUC by 37% and 1 clearance by 25%), particularly following sequential administration of paditaxel followed by epirubicin Attributed to altered distribution of epirubicin in the plasma and inhibition of P-gp by Cremophor, the vehicle of paditaxel formulation, resulting in 1 clearance Epirubicin should always be given prior to paditaxel... 

C21-Amino-Epo B [BMS-310705 (23)] is undergoing clinical evaluation in humans, but only hmited biological data are currently available in the literature for this compound. Thus, an IC50 value of 0.8 nM for growth inhibition of the human epidermoid cancer cell line KB.31 has been reported in a patent application (vs 1.2nM for Epo B under comparable experimental conditions" ). More recently, Uyar et al." have demonstrated that 50 nM BMS-310705 induces substantial apoptosis in early passage ovarian cancer cells (OC-2), which were derived from a clinical tumor sample and were refractory to paclitaxel and platinum treatment. A concentration of 50 nM of BMS-310705 (23) is clinically achievable at a dose of 10 mg/m, which is below the phase 1 maximum tolerated dose (MTD) for the compound. " BMS-310705 (23) exhibits improved water-solubility over BMS-247550 (1), which enables the use of chnical formulations not containing Cremophor-EL. ... 

Liebmann J, Cook JA, Mitchell JB. Cremophor EL, solvent for paclitaxel, and toxicity. Lancet 1993 342 1428. 

Taxol Paclitaxel Bristol Myers Squibb Cremophor EL 52.7% Ethanol 49.7% IV Infusion... 

Ibrahim, N.K. Desai, N. Legha, S. Soon-Shiong, P. Theriault, R.L. Rivera, E. Esmaeli, B. Ring, S.E. Bedikian, A. Hortobagyi, G.N. Ellerhorst, J.A. Phase I and pharmacokinetic study of ABI-007, a Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. Clin. Cancer Res. 2002, 8 (5), 1038-1044. 

Taxol (Paclitaxel) IV infusion after dilution 51% Cremophor EL... 

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