Optimal sampling time‑point for cyclosporin A concentration monitoring in heart transplant recipients

Abstract

The present study was performed to determine an optimal time-point for monitoring the concentration of the immunosuppressive drug cyclosporin A (CsA) in heart transplant patients and its efficacy in the prevention of transplant rejection. A total of 32 transplant recipients were randomly assigned for three treatment approaches. Recipients in groups A (n=11), B (n=13) and C (n=8) received oral administration of CsA at doses of 3.2, 3.5 and 4.4 mg/kg, respectively. The plasma CsA concentrations were examined at 2 h intervals over 12 h. Furthermore, their correlation with the 4 h pharmacokinetic profiles as the area under the plasma CsA concentration vs. time curve (AUC 0-4 h) were calculated The efficacy of CsA in inhibiting cardiac allograft rejection was assessed at 2 h after oral CsA intake (C2) and adverse events of the drug were examined in the C2-monitored recipients. The plasma CsA concentration rapidly increased in most recipients with a peak level detected at ~2 h after dosing. Regression analysis revealed that among all time-points assessed, the CsA had the highest correlation with the AUC 0-4 h at C2. At C2, increasing CsA doses exhibited a positive association with the measure of AUC 0-4 h. The efficacy of increasing CsA target levels at C2 in preventing heart transplant rejection was comparable, as the survival rate was 100% in all of the treatment groups. However, the proportion of recipients with side effects in group A was obviously lower than that in the other two groups. In conclusion, C2 is an ideal time-point for monitoring plasma CsA levels with a utility for individualising the next scheduled dose for each patient to ensure that target levels are maintained and achieve a high efficacy and safety of CsA therapy in heart transplant recipients (clinical trial no. 12002610).

Initial dosage optimization of ciclosporin in pediatric Chinese patients who underwent bone marrow transplants based on population pharmacokinetics

“…The immunosuppressive drug ciclosporin was initially approved for use to prevent rejection in organ transplants, such as in liver (30,31), kidney (32,33), lung (34) and heart (35,36). Additionally, ciclosporin has been approved by the US Federal Drug Association for severe psoriasis and rheumatoid arthritis treatment (37).…”

Short‐term cyclosporin A treatment improves pregnancy outcomes in patients with unexplained pregnancy loss: A prospective, open‐label, observational study

“…For patients in the CsA group, the CsA concentration needed to be determined, including the C 0 (concentration prior to medication) and C 2 (concentration after 2 h of medication) concentrations. If the C 0 concentration was less than 40 ng/ml or the C 2 concentration was higher than 400 ng/ml, the CsA dosage was adjusted under transplantation experiences 24‐26 …”

“…If the C0 concentration was less than 40 ng/ml or the C2 concentration was higher than 400 ng/ml, the CsA dosage was adjusted under transplantation experiences. [24][25][26]…”

Immunosuppressive Drugs

“…Similarly, in case of heart transplant, an ideal therapeutic dose of cyclosporine required is 250–350 ng/mL in the first 6 months accompanied by 100–200 ng/mL up to 12 months of transplantation. Same therapeutic level is maintained in case of liver transplantation ( Jia et al, 2018 ). There is a very small spectrum of effective doses of cyclosporine and concentrations consistent with severe toxicity.…”