Mycophenolate mofetil (MMF) is used for oral administration to prevent rejection in renal transplant recipients, and is rapidly converted into mycophenolic acid (MPA), the active metabolite, by hydrolysis in vivo. The area under the concentration-time curve (AUC 0-12 h ) of MPA is considered to be an effective pharmacokinetics parameter for predicting acute rejection. However, frequent blood sampling is required to calculate AUC 0-12 h , which imposes a burden on patients and providers. Therefore, we examined a limited sampling strategy (LSS) for estimation of MPA-AUC 0-12 h using only a trough level (C 0 ) and two points including C 0 in Japanese living-related renal transplant recipients with concomitant extended-release tacrolimus (ER-TAC). The present study suggests that better estimation of MPA-AUC 0-12 h can be obtained by using two points including C 0 as compared with only C 0 regardless of transplant progress. Furthermore, blood collection points showing the highest estimation of MPA-AUC 0-12 h by adding to C 0 were C 4 at pre-transplantation (Tx) and 1 month post-Tx, and C 6 at 3 months post-Tx. We conjecture that changes in renal function and serum albumin (Alb) accompanying transplant progress are aggravating factors in terms of estimation, because there was also a significant difference in the reciprocal of serum creatinine (1/Scr) and Alb between pre-Tx and post-Tx in this study. In conclusion, the present study provides useful information for effective and efficient monitoring of MPA levels in Japanese living-related renal transplant recipients.

The effects of preserving conditions and time after extraction of human teeth, as specimens for bond strength of composite resin to the dentin, were investigated by the tensile test method and scanning electron microscopy (SEM).When the teeth were stored in physiologic saline solution, bond strength at 15 minutes after extraction showed the lowest value (13kg/cm2), and at 1 to 12 weeks it was elevated to about 35kg/cm2. However pretreatment with citric acid-FeCl3 solution of dentin surface increased the bond strength 3-fold. The teeth stored in formalin for 6 months had the highest bond strength (80kg/cm2). On SEM observation of the dentin and resin surfaces following the tensile test, a clear correlation was found between range of bond strength and appearance of resin tags.

We report a case of encephalopathy seemingly caused by tacrolimus (FK506) in spite of blood concentration near the upper limit of therapeutic range. A 26-year-old man received FK506 to prevent acute graft-versus-host disease after hematopoietic stem cell transplantation. He underwent an intravenous injection of FK506 the day before transplantation (day -1). He developed headache, hypertension, nausea and vomiting from day 2 to day 3. A computed tomography scan showed a low density area with unclear border in the bilateral cerebellar hemispheres. Thereafter, these symptoms improved with discontinuation of FK506, which was strongly suggestive of encephalopathy caused by FK506. The blood concentration of FK506 at the onset of encephalopathy was 21.7 ng/mL. Although this value was slightly higher than the standard therapeutic range (10 20 ng/mL), it was within clinically acceptable range in the early stage after stem cell transplantation. This indicates that even if the blood concentration of FK506 is within the therapeutic range, encephalopathy may develop. In summary, although the blood concentration of FK506 is useful as an indicator for prevention of encephalopathy, we propose careful monitoring not only of the blood concentration but also clinical status for the detection of initial symptoms and prevention of aggravation.

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