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Cyclosporine, Whole Blood
Liquid chromatography/tandem mass spectrometry (LC/MS-MS)
Therapeutic: 100−400 ng/mL. The recommended therapeutic ranges by donor organ are as follows:
• Renal transplant: 100−250 ng/mL
• Liver transplant: 100−400 ng/mL
• Cardiac transplant: 100−400 ng/mL
• Bone marrow transplant: 200−300 ng/mL
Cyclosporine is an immunosuppressive agent derived from Tolypocladium inflatum gams, a fungus originally isolated from a Norwegian soil sample. The agent is used extensively to control rejection of organ transplants, especially of liver, heart, or kidney. The effectiveness of cyclosporine results from specific and reversible inhibition of immunocompetent lymphocytes in the G0 and G1 phase of the cell cycle. T-lymphocytes are preferentially inhibited. The T-helper cell is the main target, although the T-suppressor cell may also be suppressed. Cyclosporine also inhibits lymphokine production and release, including interleukin-2.
Monitoring blood levels is imperative because the pharmacokinetics of cyclosporine are not only complex but vary over time in the same patient; thus, blood levels cannot be well predicted from dosing schedules. Furthermore, this drug has a narrow therapeutic window and significant toxicity at levels above that range.
Renal toxicity with eventual renal failure is the most severe complication. Other assays to assess renal function (ie, BUN, creatinine clearance) should be ordered along with cyclosporine level, since toxicity may begin even with “acceptable” blood levels. Other toxicities include hypertension, convulsions, tremors, pulmonary edema, and an increased risk of lymphoma.
Drugs that enhance the potential toxicity of cyclosporine, include aminoglycoside antibiotics, amphotericin B, acyclovir, ketoconazole, lovastatin, NSAIDs, and ranitidine. Agents that are CYP3A3 and CYP3A4 inhibitors raise cyclosporine levels by decreasing biotransformation. These include methylprednisolone, amphotericin B, cimetidine, amiodarone, fluoxetine, protease inhibitors, erythromycin, and grapefruit juice. Agents that increase hepatic metabolism and, thus, lower cyclosporine levels include phenobarbital, phenytoin, carbamazepine, rifampin, trimethoprim, and St John's wort.
Because results vary depending on the method and cyclosporine antibody employed (monospecific or polyspecific), it is best for a given patient's specimens to be analyzed at a single laboratory to eliminate as many assay-dependent variables as possible.
Half-life of elimination; Oral: May be prolonged in patients with hepatitis impairment and may be shorter in pediatric patients due to the higher metabolism rate. The elimination profile of cyclosporine is biphasic. An early elimination phase with an apparent half-life that typically ranges from three to seven hours is followed by a slower elimination of phase with an apparent half-life ranging from 18 to 25 hours. The peak concentration is reached in four to six hours.
|Order Code||Order Code Name||Order Loinc||Result Code||Result Code Name||UofM||Result LOINC|
|706556||Cyclosporine, Blood||55805-6||706559||Cyclosporine, LC-MS/MS||ng/mL||55805-6|
|Reflex Table for Cyclosporine, LC-MS/MS|
|Order Code||Order Name||Result Code||Result Name||UofM||Result LOINC|
|Reflex 1||007000||See below:||007000||See below:||N/A|