Because of the uncertain role that these metabolites play in immunosuppression and drug side effects, and because of the very high level of these metabolites in patients with cholestasis, we rely on the HPLC assay using whole blood as the specimen. A trough level is obtained at a time when the blood or plasma concentration is the lowest. In most cases this is within one hour prior to the next drug dose. One of the most important side effects of cyclosporine is dose dependent nephrotoxicity. The most consistent findings are tubular dilation and epithelial cell vacuolation with tubular destruction.
Interstitial fibrosis is found in long standing toxicity.
Among the mechanisms of nephrotoxicity, reduced renal blood flow appears to the most consistently documented. Some workers have noted that an alpha sympathomimetic effect was ameliorated by renal denervation or by Dibenzalene or prazosin administration. Other mechanisms may include a mediated reduction in the production of renal cortical vasodilator PGI2 relative to vasoconstrictor thromboxane A2. A number of prescription drugs have been found to interact with cyclosporine to intensify many of its side effects or conversely lower the cyclosporine blood concentration to nontherapeutic ranges. Listed below are the known drugs which adversely interact with cyclosporine.