9342. Cyclosporine

Cyclosporine is a medication from the group of immunosuppressants. It is used in patients who have undergone organ and tissue transplantation to prevent rejection. Given the drug's relatively high toxicity and narrow therapeutic window, accurate selection of the optimal dosage is essential. This is best achieved by monitoring the drug concentration in the blood over time.

The test is used to assess blood cyclosporine levels in patients taking the medication following organ transplantation.

Pharmacotherapeutic Group
Immunosuppressants. Calcineurin inhibitors.

Pharmacodynamics
Selective immunosuppressant that inhibits calcineurin activation in lymphocytes during the G0 or G1 phase of the cell cycle. In this way, it prevents T-lymphocyte activation and, at the cellular level, antigen-dependent release of lymphokines, particularly interleukin-2 (a T-lymphocyte growth factor). It impairs the differentiation and proliferation of T cells involved in transplant rejection. Cyclosporine acts specifically and reversibly on lymphocytes. Unlike cytostatics, it does not suppress hematopoiesis or affect phagocyte function.

Pharmacokinetics
It is absorbed relatively rapidly and completely from the gastrointestinal tract. The time to reach Cmax after oral administration ranges from 1 to 6 hours. Absolute bioavailability is 20–50%. Plasma protein binding (predominantly to lipoproteins) is approximately 90%. It is distributed predominantly outside the bloodstream, although it is also detected in erythrocytes, granulocytes, and lymphocytes. In the liver, it undergoes hydroxylation and N-demethylation with the participation of the cytochrome P450-dependent monooxygenase system.

All metabolites (more than 15) retain the intact parent structure, and some retain weak immunosuppressive activity. The elimination half-life (T½) ranges from 6.3 to 20.4 hours. It is excreted mainly in the bile; approximately 6% of the dose is detected in urine, with less than 1% excreted unchanged. A steady-state concentration is reached 2–4 days after dose adjustment. During the early post-transplant period, monitoring is performed 2–3 times a week, while during maintenance therapy it is performed 1–2 times a month.

Overdose
Impaired renal function may develop, which is likely to be reversible after discontinuation of the medication.

• Monitoring cyclosporine concentration in the blood, particularly when medications with CYP3A4-inducing or CYP3A4-inhibiting properties are prescribed concomitantly.
• Selection and adjustment of the optimal dose to achieve immunosuppression with minimal toxicity.
• Detection of toxic drug levels.
• Assessment of drug interactions.
• Monitoring adherence to the prescribed treatment regimen.

• Venous blood

In order to exclude factors that may affect the test results, we recommend to follow the preparation rules: