Potential neurotoxicity of the solvent vehicle for cyclosporine.

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.

• Publication year

  1994

• Venue

  Journal of Pharmacology and Experimental Therapeutics

• Publication date

  1994-02-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/s0022-3565(25)38962-7PMID 8113961
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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