C2 single-point sampling to evaluate cyclosporine exposure in long-term renal transplant recipients

Clinical outcomes and C2 cyclosporin monitoring in maintenance renal transplant recipients: 1 year follow-up study

“…That could be the expression of the presence of chronic allograft nephropathy due to inadequate immunosuppression or, alternatively, to the reduction of CsA dose and/or the introduction of a third drug to control graft function deterioration or other undesirable side effects of CsA. Some researchers have found that the development of chronic rejection was related to low CsA exposure measured by AUC or C2 [18,19], but their data showed neither whether low CsA exposure was before or after the development of graft dysfunction nor whether some therapeutic measure was taken such as CsA dose reduction. Others found no relationship between C2 levels and chronic allograft nephropathy [20].…”

Therapeutic Monitoring of Calcineurin Inhibitors for the Nephrologist

“…In a group of long-term patients who were maintained with C 0 levels of 206 Ϯ 75 ng/ml, C 2 levels ranged from 140 to 2440 ng/ml. Patients with progressively rising serum creatinine values had lower C 2 levels (mean 492 Ϯ 327 versus 1054 Ϯ 579 ng/ml) and AUC 0 to 12 (mean 3798 Ϯ 1145 versus 6462 Ϯ 1886 g/h per L), and most had evidence of CAN on biopsy (53). This suggests that underexposure to cyclosporine in long-term transplant recipients is a risk factor for CAN and that C 2 monitoring might identify these patients.…”

Renal Biopsy Findings in Children Receiving Long-Term Treatment with Cyclosporine A Given as a Single Daily Dose

“…We have confirmed in a previous study that most NS children given Neoral ® before breakfast show a stable absorption profile of the drug, and also reported that the peak blood levels of the drug are usually achieved between 1 and 2 hrs post-dosing. Thus, we speculated that the CsA blood level measured between 1 and 2 hrs post-dosing (peak blood level) in pediatric patients might show a reliable correlation with the treatment efficacy and toxicity (Nakahata et al 2005;Tanaka et al 2005), as reported for the C 2 (2 hrs post-dosing) blood level in adult patients (Citterio et al 2001). Indeed, we have confirmed that in most SDNS patients who receive CsA according to our current treatment protocol a calculated 0-4 hrs area-under-time-concentration curve (AUC 0-4 ) of CsA of around 2,000 ng hr/ml (data not shown), an adequate value according to a previous report (Uchida et al 2004), is achieved.…”

“…Because of the absence of a reliable correlation between the trough blood level of CsA (Neoral ® ) and the clinical events in renal transplant patients, it has been suggested that measurement of C 2 (level 2 hrs after the drug administration) might be a simple and useful method for the pharmacokinetic monitoring of CsA; this is based on the observation of a good correlation between the C 2 and the AUC 0-12 (Citterio et al 2001). We previously reported on the potential usefulness of our current single daily dose protocol for CsA (Neoral ® ) treatment.…”

“…Following the widespread clinical use of Neoral ® , a new oral microemulsion formulation of cyclosporine A (CsA), in place of Sandimmun ® , it has been reported that the clinical efficacy of the drug is most significantly related to the peak blood level of the drug in renal transplant patients (Citterio et al 2001). In this context, we previously reported on the usefulness of low-dose CsA (Neoral ® ) given as a single daily dose, which yielded higher peak blood levels without associated elevation of the trough blood levels of the drug, in selected patients of nephrotic syndrome (NS) in whom CsA administration by the conventional twice-daily administration protocol was associated with a poor steroid-sparing effect Kudo et al 2005).…”