Potential neurotoxicity of the solvent vehicle for cyclosporine

Anthony John Windebank, M. D. Blexrud, P. C. De Groen

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Nervous system complications resulting from i.v. administration of cyclosporine (CS) are especially frequent in liver transplant recipients. Because CS is insoluble in water, the i.v. preparation is formulated in a polyoxyethylated castor oil and ethyl alcohol. Rat dorsal root ganglion neurons exposed in vitro to the i.v. preparation exhibited axonal swelling and degeneration. No effect of CS (dissolved directly in serum) was seen on testing individual components of the i.v. solution. However, 0.1% polyoxyethylated castor oil (volume of solute/volume of solvent) produced axonal swelling and degeneration and 0.001% polyoxyethylated castor oil produced demyelination in vitro. Polyoxyethylated castor oil is manufactured by reacting castor oil with ethylene oxide, and we speculate that residual ethylene oxide or a polymerization product may be responsible for the in vitro neurotoxicity. Although little is known about the pharmacokinetics of polyoxyethylated castor oil, plasma levels of 0.001 to 0.01% polyoxyethylated castor oil (volume of solute/volume of solvent) are probably achieved with therapeutic doses of the i.v. CS preparation.

Original languageEnglish (US)
Pages (from-to)1051-1056
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume268
Issue number2
StatePublished - 1994

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Castor Oil
Cyclosporine
Ethylene Oxide
Spinal Ganglia
Demyelinating Diseases
Polymerization
Nervous System
Ethanol
Pharmacokinetics
Neurons
Water
Liver
Serum

ASJC Scopus subject areas

  • Pharmacology

Cite this

Potential neurotoxicity of the solvent vehicle for cyclosporine. / Windebank, Anthony John; Blexrud, M. D.; De Groen, P. C.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 268, No. 2, 1994, p. 1051-1056.

Research output: Contribution to journalArticle

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