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DOI: 10.1055/s-0031-1296274
Comparative study of peripheral neurotoxicity after injection of two different paclitaxel formulations in rats
Publikationsverlauf
Publikationsdatum:
02. Dezember 2011 (online)
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Abstract
Paclitaxel Inj. [NK] (test; paclitaxel, CAS 33069-62-4) is a generic version of the drug from the originator (reference). Both drugs contain the same active ingredient and showed identical pharmacokinetics in patients in the previous study; however, these two drugs may have different safety profiles because they contain different inactive ingredients. Thus, in this study, peripheral neurotoxicity, one of the dose-limiting toxicities of the reference, was compared between the test and the reference in rats electrophy-siologically and histopathologically. In a nerve conduction study, the amplitude of the caudal sensory nerve action potentialdecreased significantly after either the test or the reference administration, compared with the amplitude after saline administration, but no significant differences were observed between the two drugs. Histopathologically, apparent degeneration of the myelinated fibers in the sciatic and the sural nerves was seen after either the test or the reference injection, compared with after saline injection, but no apparent differences were observed between the two formulations. These results suggest that no significant difference in peripheral neurotoxicity exists between the test and the reference in rats.
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References
- 1 Carney DN. Chemotherapy in the management of patients with inoperable non-small cell lung cancer. Semin Oncol. 1996; 23: 71-5
- 2 Crown J, O'Leary M. The taxanes: an update. Lancet. 2000; 355: 1176-8
- 3 Rowinsky EK, Chaudhry V, Cornblath DR, Donehower RC. Neurotoxicity of Taxol. J Natl Cancer Inst Monogr. 1993; 107: 15
- 4 Rowinsky EK, Donehower RC. Paclitaxel (taxol). N Engl J Med. 1995; 332: 1004-14
- 5 Lipton RB, Apfel SC, Dutcher JP, Rosenberg R, Kaplan J, Berger A et al Taxol produces a predominantly sensory neuropathy. Neurology. 1989; 39: 368-73
- 6 Gelderblom H, Verweij J, Nooter K, Sparreboom A. Cremo-phor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer. 2001; 37: 1590-8
- 7 van OTellingen, Huizing MT, Panday VR, Schellens JH, Nooijen WJ, Beijnen JH et al Cremophor EL causes (pseu-do-) non-linear pharmacokinetics of paclitaxel in patients. Br J Cancer. 1999; 81: 330-5
- 8 Sagara Y, Rai Y, Matsuyama Y, Baba S, Tamada S, Ando M. Comparison of the pharmacokinetics and safety of a paclitaxel injection NK and taxol injection in breast cancer patients. Gan To Kagaku Ryoho. 2009; 36: 247-50
- 9 Goda R, Yamaguchi T, Yamashita T, Yazawa Y, Kawashiro T, Arai S et al Plasma concentration in dogs, compatibilityand drip rate of Paclitaxel Inj. 30 mg/5mL [NK]. Jap J Med Pharmaceut Sci. 2006; 56l: 563-70
- 10 Chaudhry V, Rowinsky EK, Sartorius SE, Donehower RC, Cornblath DR. Peripheral neuropathy from taxol and cis-platin combination chemotherapy: clinical and electrophysiological studies. Ann Neurol. 1994; 35: 304-11
- 11 Sahenk Z, Barohn R, New P, Mendell JR. Taxol neuropathy. Electrodiagnostic and sural nerve biopsy findings. Arch Neurol. 1994; 51: 726-9
- 12 Apfel SC, Lipton RB, Arezzo JC, Kessler JA. Nerve growth factor prevents toxic neuropathy in mice. Ann Neurol. 1991; 29: 87-90
- 13 Cavaletti G, Cavalletti E, Montaguti P, Oggioni N, De Negri O, Tredici G. Effect on the peripheral nervous system of the short-term intravenous administration of paclitaxel in the rat. Neurotoxicology. 1997; 18: 137-45
- 14 Cavaletti G, Tredici G, Braga M, Tazzari S. Experimental peripheral neuropathy induced in adult rats by repeated intraperitoneal administration of taxol. Exp Neurol. 1995; 133: 64-72
- 15 Cliffer KD, Siuciak JA, Carson SR, Radley HE, Park JS, Lewis DR et al Physiological characterization of Taxol-induced large-fiber sensory neuropathy in the rat. Ann Neurol. 1998; 43: 46-55
- 16 Jamieson SM, Liu JJ, Connor B, Dragunow M, McKeage MJ. Nucleolar enlargement, nuclear eccentricity and altered cell body immunostaining characteristics of large-sized sensory neurons following treatment of rats with paclitaxel. Neurotoxicology. 2007; 28: 1092-8
- 17 Persohn E, Canta A, Schoepfer S, Traebert M, Mueller L, Gilardini A et al Morphological and morphometric analysis of paclitaxel and docetaxel-induced peripheral neuropathy in rats. Eur J Cancer. 2005; 41: 1460-6
- 18 Peters CM, Jimenez-Andrade JM, Jonas BM, Sevcik MA, Koewler NJ, Ghilardi JR et al Intravenous paclitaxel administration in the rat induces a peripheral sensory neuropathy characterized by macrophage infiltration and injury to sensory neurons and their supporting cells. Exp Neurol. 2007; 203: 42-54
- 19 Mimura Y, Kato H, Eguchi K, Ogawa T. Schedule dependency of paclitaxel-induced neuropathy in mice: a morphological study. Neurotoxicology. 2000; 21: 513-20
- 20 Freireich EJ, Gehan EA, Rall DP, Schmidt LH, Skipper HE. Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man. Cancer Chemother Rep. 1966; 50: 219-44