Risk factors for cisplatin-induced nephrotoxicity and potential of magnesium supplementation for renal protection.

BACKGROUND: Nephrotoxicity remains a problem for patients who receive cisplatin chemotherapy. We retrospectively evaluated potential risk factors for cisplatin-induced nephrotoxicity as well as the potential impact of intravenous magnesium supplementation on such toxicity. PATIENTS AND METHODS: We reviewed clinical data for 401 patients who underwent chemotherapy including a high dose (≥60 mg/m2) of cisplatin in the first-line setting. Nephrotoxicity was defined as an increase in the serum creatinine concentration of at least grade 2 during the first course of cisplatin chemotherapy, as assessed on the basis of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The severity of nephrotoxicity was evaluated on the basis of the mean change in the serum creatinine level. Magnesium was administered intravenously to 67 patients (17%). RESULTS: Cisplatin-induced nephrotoxicity was observed in 127 patients (32%). Multivariable analysis revealed that an Eastern Cooperative Oncology Group performance status of 2 (risk ratio, 1.876; P = 0.004) and the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) (risk ratio, 1.357; P = 0.047) were significantly associated with an increased risk for cisplatin nephrotoxicity, whereas intravenous magnesium supplementation was associated with a significantly reduced risk for such toxicity (risk ratio, 0.175; P = 0.0004). The development of hypomagnesemia during cisplatin treatment was significantly associated with a greater increase in serum creatinine level (P = 0.0025). Magnesium supplementation therapy was also associated with a significantly reduced severity of renal toxicity (P = 0.012). CONCLUSIONS: A relatively poor performance status and the regular use of NSAIDs were significantly associated with cisplatin-induced nephrotoxicity, although the latter association was marginal. Our findings also suggest that the ability of magnesium supplementation to protect against the renal toxicity of cisplatin warrants further investigation in a prospective trial.

[TDM management system for contribution to proper use of anti-mRSA drugs--establishment of cooperation support system between pharmacy and clinical laboratory in hospital].

In team medicine, highly specialized pharmacists have recently been in demand. As one of the specialties, there is therapeutic drug monitoring (TDM). It is important for the optimal dosing of a wide range of drugs. In our hospital, a TDM service was started in 1987 at the clinical laboratory. A clinical laboratory technologist with the license of a pharmacist has performed administration plans for anti-methicillin-resistant Staphylococcus aureus (MRSA) drugs, vancomycin, teicoplanin, and arbekacin. In particular, the pharmacist in charge of TDM services, a TDM-specialized pharmacist, plays a central role in administration plans for anti MRSA drugs. Furthermore, we examined the active use of the TDM service to expand pharmaceutical care. Therefore, at first, we have worked in partnership with the clinical laboratory, as it is called the "Cooperation Support System", since September 2010. As a result, after the introduction of this system, from August 2011 to July 2012, the rate that the doctor referred to the administration plan was markedly improved by approximately 90%. We have been able to enhance TDM in practical training for pharmacology as an extension of this system. We thought that drug therapy can be performed more appropriately by increasing the number of executions of TDM in the future. For drug therapy to be done more appropriately, efforts made through cooperation with the clinical laboratory are essential for an effective TDM system. Naturally, an effective TDM process requires a collaborative, multidisciplinary approach with input from doctors, nurses, and clinical pharmacists.

Studies on the variation in clinical laboratory data and safety evaluation of pharmaceuticals.

The safety of pharmaceuticals has become increasingly important not only in daily medical treatment but also in clinical trials. Although clinical laboratory data are more objective than clinical symptoms, the determination as to whether they indicate abnormal variations depends largely upon the clinical judgment of physicians. The process of determination has not been sufficiently objectified. The present study investigated the indices of criteria for variations in clinical laboratory data obtained in clinical trials. Then, detection rates of abnormal variations were compared between our determination method that employs the reference change value (RCV) expressing the width of biological variation for each test component and conventional determination methods. The study also demonstrated that by combining standard values and the RCV for determination, abnormal variations were found at a rate greater than 50%. The method we propose was applied to the safety evaluation of pharmaceuticals. In clinical trials on the antiviral drug ribavirin administered alone, components of laboratory tests were selected that should be noted in studies on its effects. Expect for decreases in red blood cell counts and hemoglobin values, which are closely associated with anemic symptoms and well known to hepatologists, the increasing trend in platelet counts and decreasing trend in albumin were found to be laboratory test components that should be paid attention to, even though they may not be obvious.