[Purpose]To prevent acute rejection for renal transplantation, a combination immunosuppressive therapy of calucineurin inhibitors, antimetabolites, and steroids is usually provided. In the immunosuppressive therapy which uses high-dose mizoribine (MZ: 6 mg/ kg/ day) for antimetabolites, referred to as high-dose MZ therapy, it has been a problem that the individual difference of the blood concentration of MZ is large. MZ is a renal excretion drug, but the change between the individual of the absorption factor is remarkable, and the absorption of MZ becomes the factor which has an influence on the blood concentration following renal function. However, long-term changes in MZ absorption in individual patients have not been studied. We thus evaluated intra-individual MZ absorption changes.[Methods]Our study included patients receiving high-dose MZ therapy after living renal transplantations, performed between March 2007 and December 2014, and whose blood MZ data at 2 weeks, 4 weeks and 1 year postoperatively were available. We evaluated changes in “apparent absorption” defined as the area under the blood concentration-time curve corrected with renal function and dose (AUC・eGFR/ Dose) of MZ in each patient. We also evaluated how patient demographics (age, male/female ratio, concomitant CNI, whether the patient had been on dialysis before the operation, preoperative dialysis duration, preoperative glucose metabolism) affected the changes in “apparent absorption”.[Results]“Apparent absorption” was significantly increased at 4 weeks after renal transplantation, as compared with 2 weeks thereafter (mean rate of change, 130%) and was significantly decreased at 1 year as compared with 4 weeks after receiving a donor kidney (mean rate of change, 85%). Patient demographics did not affect “apparent absorption”. [Discussion]Our study showed the duration of MZ treatment to affect absorption changes with high-dose MZ therapy. Then this result, it was confirmed that enforcement of therapeutic drug monitoring was important to give high-dose MZ therapy appropriately. Moreover, we propose that when planning to administer MZ, we should take particular note of the duration of MZ treatment.
Objective: The dose of tenofovir disoproxil fumarate (TDF) requires an adjustment in patients with renal dysfunction. However, a combination tablet containing TDF is often prescribed to improve medication adherence, which makes TDF dose adjustment difficult. In fact, the discontinuation of TDF has been observed based on the estimated glomerular filtration rate (eGFR) decline not adjusted for body surface area (BSA) in our hospital. Therefore, we focused on evaluating the eGFR without a BSA adjustment (unadjusted eGFR) at the start of TDF administration to investigate the association between TDF exposure and the risk of unadjusted eGFR decline.Method: We retrospectively reviewed the clinical records of 21 patients infected with the human immunodeficiency virus (HIV) and receiving combination anti-retroviral therapy including TDF at our hospital between April 2005 and May 2014. Patients were divided into two groups based on the unadjusted eGFR: the more than (MT) and less than (LT) 80 mL/min groups at the start of TDF therapy. We compared the unadjusted eGFR, and other relevant factors between the two groups.Result: Of the 13 patients in the MT group, 12 tolerated TDF while only two of the eight patients in the LT group did, which indicated a significant difference between the two groups. Further, in patients who corresponded to a low-dose standard, a significant correlation was observed between the unadjusted eGFR level and TDF treatment duration.Consideration: In this study, the administration of TDF caused an unadjusted eGFR decline in patients (eGFR 50-80 mL/min), making the continuous administration of TDF difficult. Therefore, we recommended the implementation of careful medication consultation as well as drug fostering and evolution of TDF dose adjustment in high-risk patients (eGFR 50-80 mL/min).
The normal antimicrobial dose in Japan is often lower than that administered overseas, and a similar tendency is also recognized in the treatment of dialysis patients. We investigated the safety and efficacy of cefalexin for exit-site infections through a retrospective review of peritoneal dialysis patients. The study subjects were peritoneal dialysis patients with exit-site infections who were taking cefalexin ( 500 mg ) orally twice a day in accordance with the recommendations of the International Society for Peritoneal Dialysis from January 2013 to December 2014. We evaluated each patient with multiple treatments during the research period; in total, the study had 13 patients and 20 administrations available for analysis. The average values for patient age, body weight, and peritoneal dialysis period were 55.9 ± 14.1 years, 65.4 ± 18.6 kg, and 12.4 ± 12.0 months, respectively. Causative bacteria were not identified in approximately half of the patients, but when identified, methicillin-sensitive Staphylococcus aureus was found most frequently. The average administration period for cefalexin was 20.1 ± 8.7 days. We observed a favorable therapy effect among the patients, with a 95.0% (19 / 20) efficacy rate. Therapy failure occurred in one patient for whom an ineffective antimicrobial agent was changed, as directed by the attending doctor. In terms of safety, an attending doctor clearly indicated in the medical records that cefalexin caused adverse effects, including mild diarrhea in one patient. There were no patients with abnormal laboratory values. Potential limitations of this study include the control group is not configured to evaluate the effectiveness. But since no obvious severe adverse effects were observed, even after the administration of cefalexin. Our results suggest that the drug could be administered safely.