Pre– and postrenal transplantation pharmacokinetics of cyclosporine microemulsion

Abstract 

The availability of a microemulsion formulation (ME) of cyclosporin (CyA) displays improved bioavailability and reduced inter and intra-patient variability, resulting in improved long-term outcomes. Recent developments in therapeutic drug monitoring stress the need to optimize peak drug levels during the early posttransplant period to obtain long-term benefit.

Method

We studied early CyA-ME pharmacokinetics, comparing pre- versus immediate posttransplant values, to assess predictability of pre-transplant profiles in 22 patients including 3 diabetics. An 8 mg/kg per day amount in two divided doses was administered, for 5 days pretransplant and 10–14 days posttransplant before performing the pharmacokinetic studies. Drugs interacting with CyA metabolism/absorption were withdrawn and patients with liver disease were excluded the CyA level monitoring used a 5-point blood sampling (at 0 hours, 1 hours, 2 hours, 3 hours, and 4 hours post-dose) The study compared actual concentrations at each individual time and the limited 0–4 hour AUC.

Results

The paired values at each point pre- and posttransplant were: C0 = 171 ± 63 and 215 ± 112, C1 = 723.86 ± 345 and 1239.95 ± 415, C2 = 972 ± 185 and 1249.95 ± 336, C3 = 822 ± 242 and 942.7 ± 286, and C4 = 601.54 ± 190 and 670.5 ± 208 ng/mL respectively. The C1 and C2 values were significantly higher posttransplant (P = .008 and 0.0045 respectively), suggesting a steeper absorption phase, a conclusion consistent with the higher 0–4 hour AUC posttransplant (P = .0089). However, linear regression analysis of pre- versus posttransplant values showed poor correlations.

Conclusion

CyA absorption is significantly lower among patients on maintenance hemodialysis and showed no predictive correlation with posttransplant levels. The possible role of uremia in retarding absorption which may have clinical significance for primary graft dysfunction, needs further evaluation.