Thus, samples should be analysed within 6 months of storage at ?20C. Pharmacokinetic and pharmacodynamic analysis MPA PK guidelines were derived from individual plasma concentrationCtime profiles by using standard non\compartmental equations. MPA PK, baseline IMPDH activity, as well as MPA\induced IMPDH inhibition were studied. Results The IMPDH activity pre\transplantation did not differ between seniors and younger individuals. Neither IMPDH activity pre\transplantation nor maximum IMPDH inhibition was significantly correlated with the individuals’ age. The area under the MPA plasma concentrationCtime curve (AUC0C12h) and the area under the effect (IMPDH activity)Ctime curve (AEC0C12h) from 0 to 12?h were also not significantly different between the two organizations. We found no significant variations in EC50 and guanine nucleotide synthesis in proliferating T\ and B\lymphocytes. Recent studies shown that a high IMPDH activity both before and after transplantation is definitely associated with an increased risk for biopsy\verified acute rejection 24, 25, 26. However, the effect of age was not investigated in these studies and it is at present unfamiliar if age\related changes in the PK Rabbit polyclonal to RABAC1 and/or PD of MPA are one of the reasons for the different outcomes of seniors and more youthful transplant recipients. Here, we statement a combined PK and PD analysis of MPA performed inside a cohort of individuals treated with MMF. Patients were followed over time, and sampled repeatedly, both before and during the 1st 6 months after kidney transplantation. Age\related variability in MPA PK, baseline IMPDH activity, as well as MPA\induced IMPDH inhibition were analyzed. The hypotheses of the present study were: (1) the PK of MPA is different in elderly compared with more youthful transplant recipients; (2) seniors individuals have a lower baseline (before transplantation) IMPDH activity; and (3) seniors kidney transplant recipients encounter a greater degree of IMPDH inhibition following treatment with MMF as compared with more youthful transplant recipients. Materials and methods Study design and human population A total of 101 individuals were recruited for this study from April 2006 to September 2007. Each individual experienced received a kidney transplant with an uncomplicated immediate post\operative recovery within the 1st day after the transplantation and were becoming treated with MMF. All surgeries were carried out in the Erasmus MC, University or college Medical Center, Rotterdam, The Netherlands. For 80 of the 101 individuals, a full 12?h curve consisting of six blood samples about VU 0364439 day 6.0 was available for measurement of both MPA plasma concentrations and IMPDH activity. The additional 21 individuals were excluded from your analysis investigating the area under the MPA plasma concentrationCtime curve (AUC0C12h) and the area under the effect (IMPDH activity)Ctime curve (AEC0C12h) from 0 to 12?h, because of their incomplete 12?h curve samples. A full area under the curve (AUC0C 12h and AEC0C12h) was acquired at day time 6 after surgery, with samples taken at predose, 0.5, 1, 2, 6, and 12?h after oral intake of MMF. On weeks 3, 7 and 20 post\transplantation, limited sampling AUCs (two samples, acquired in the pre\dose time point and 120 moments thereafter) were collected. All blood samples were analysed for MPA plasma concentration and IMPDH activity in the laboratory of the hospital pharmacy. All individuals received triple immunosuppressive therapy, including tacrolimus (Prograft?, Astellas Pharma, Leiderdorp, The Netherlands), mycophenolate mofetil (Cell\Cept?, Roche Pharma, Woerden, The Netherlands) and prednisone. All individuals were treated with 1000?mg MMF b.i.d., except for two individuals who received 500?mg MMF b.i.d. at the time of sampling. Doses and predose concentrations of tacrolimus VU 0364439 are outlined in Table?1. All individuals received a fixed\dose prednisone of 20?mg once daily. Antithymocyte globulin (ATG, Genzyme Corp.) induction therapy was given to 23 individuals (Table?1). The study was authorized by the Local Ethics Committee of Erasmus MC, Rotterdam, The Netherlands, and complied with the Declaration of Helsinki. All individuals offered written educated consent between April 2006 and September 2007. We previously reported data from this cohort of individuals on the influence of solitary nucleotide polymorphisms of the IMPDH type II gene on between\patient variations in IMPDH activity 27. For this analysis VU 0364439 on the data set of the original study, no additional educated consent of individuals was.
Categories