Limited sampling strategies using Bayesian estimation or multilinear regression for XXXX AUC(0-12) monitoring in cardiac transplant recipients over the first year post-transplantation.

@entity1 @entity205 @entity24523 @entity44625
OBJECTIVE: The aim of this study was to develop routinely applicable limited sampling strategies for assessing @entity205 (CsA) AUC(0-12 h), and possibly other exposure indices such as AUC(0-4 h) and C(max), in heart transplant @entity1 over the first year post-transplantation. METHODS: First, the individual pharmacokinetics (PKs) of 14 adult heart-transplant @entity1 receiving Neoral were assessed at three post-transplantation periods, at the end of the first week (W1), the third month (M3) and the first year (Y1). To fit blood concentrations, a @entity24523 model specially developed for oral CsA was applied. Second, two statistical methods were compared for AUC(0-12 h) estimation using a limited sampling strategy (maximum of three blood samples): multiple regression analysis (MR) and Bayesian estimation (BE). RESULTS: No significant difference was observed between the individual @entity24523 parameters at M3 and Y1, so population modelling was performed taking as a whole the concentration data collected at M3 and Y1. On the contrary, a significant difference ( P<0.05) was found for the C2/dose ratio between @entity44625 (mean+/-SD =5.47+/-2.33; 7.78+/-1.05; 6.98+/-2.17 ml(-1 )for @entity44625 , respectively). Also, C(max)/dose and A were found significantly lower at W1 than at M3 ( P<0.01 and P<0.005, respectively), while lambda(1) was significantly higher at W1 than at both M3 and Y1 ( P<0.01). Using three sampling times (t0 h, t1 h and t3 h), BE allowed an accurate prediction of AUC(0-12 h) (mean bias =3.06+/-12.16%; +1.50+/-1.61%; and -0.20+/-11.42% at @entity44625 , respectively), AUC(0-4 h )and C(max). MR led to satisfactory estimation of AUC(0-12 h) using only two blood samples collected 2 h and 6 h post-dose (R=0.956-0.993; bias =-5.22 to +4.41; precision =6.38 to 9.90%), but this method is unable to estimate any other exposure index and requires strict respect of sampling times, contrary to BE. CONCLUSION: Neoral monitoring based on full or abbreviated AUC is possible using BE or MR in heart transplant @entity1 over the first year post-transplantation. BE provides a good description of the individual @entity24523 profiles and thus might be useful not only in case of potential discrepancies between C2 and clinical findings, but also for clinical trials aimed at finding optimum @entity24523 monitoring in heart recipients.
