An accurate estimate of the renal function is necessary for the precise therapeutic drug monitoring of anti-MRSA drugs such as vancomycin, arbekacin and teicoplanin, which are eliminated by the kidneys. In clinical practice, the measurement of endogenous serum substances in order to estimate the glomerular filtration rate (GFR) is commonly performed, and the serum creatinine concentration has become the most commonly used serum marker of renal function. However, the serum creatinine concentration is affected by age and gender. As a result, the measurement of serum creatinine concentration can lead to an overestimation of GFR, especially in the elderly. In recent years, it has been reported that the serum cystatin C concentration is not influenced by gender or age, so serum cystatin C concentration is a better marker of renal function than serum creatinine concentration. A recent meta-analysis demonstrated that the serum cystatin C concentration was a better renal function marker for detecting the GFR than the conventional measurement of the serum creatinine concentration, and several formula using the cystatin C concentration have also recently been reported to accurately estimate GFR. Recent studies have reported that the serum cystatin C concentration is a better marker of the clearance of drugs eliminated by the kidneys than the serum creatinine concentration. In this article, we review the application of cystatin C in the drug administration plan of anti-MRSA drugs.

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It is important for proper use of prescription drugs to investigate adverse effects and drug-drug interactions in a case series of patients whom pharmacists encounter in clinical practice. If several risk factors for adverse effects and drug-drug interactions are identified by such investigations, they could be applied to predicting and preventing drug-induced adverse events. This paper describes an investigation of a case series to determine the risk factors in four examples, drug-drug interaction of oxycodone – voriconazole, tacrolimus – lansoprazole, and tizanidine – CYP1A2 inhibitors and Shakuyaku-Kanzo-To induced pseudoaldosteronism. The impact of the research outcomes is also discussed for indications on how to take the medicine on the package-insert of each drug.

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No antiemetic therapies of aprepitant have been established for continuous administration of anticancer drugs across multiple days. We investigated the efficacy of using aprepitant for 3 days from Day 2 of 5-day ifosfamide administration in patients with osteosarcoma. Between December 1, 2008 and November 30, 2010, patients with osteosarcoma receiving ifosfamide therapy were allocated to either a control group or an aprepitant group. We retrospectively investigated the proportion of patients with no emetic episodes, the proportion of patients with complete response (defined as no emetic episodes and no use of rescue medication) and adverse events. We divided the proportion of patients with no emetic episodes and the proportion of patients with complete response into three periods (Days 1-5, Days 6-10 and Days 1-10), then evaluated the results. The proportion of patients with no emetic episodes was significantly higher in the aprepitant group than in the control group (during Days 1-5, 100% vs. 58.8%, p=0.012, during Days 1-10, 91.6% vs. 41.1%, p=0.007, respectively). The proportion with complete response tended to be higher in the aprepitant group, but no significant difference between groups was identified. A tendency toward decreased adverse events was also seen in the aprepitant group compared to the control group. These results suggest that administration of aprepitant for 3 days from Day 2 of anticancer drug administration can prevent emetic episodes with ifosfamide therapy. Establishment of appropriate antiemetic therapies may thus facilitate continuous administration of anticancer drugs.

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No previous study has calculated the dose-conversion ratios in patients undergoing opioid rotation from a continuous intravenous infusion of morphine hydrochloride (continuous intravenous morphine) to orally administered oxycodone sustained-release tablets, frequently used clinically. We retrospectively estimated the dose-conversion ratios in 24 patients with gastrointestinal cancer who underwent opioid rotation from continuous intravenous morphine to oxycodone sustained-release tablets from October 2003 to October 2008. All patients met both of the following conditions on at least 3 consecutive days during the 10 days after rotation: 1) the basic dose of oxycodone sustained-release tablets (basic dose) was unchanged; and 2) the difference in the daily number of rescue doses was 1 or less as compared with immediately before rotation. The dose-conversion ratios were calculated by regression line analysis from the relation between “the basic dose of continuous intravenous morphine immediately before opioid rotation” and “the basic dose of oxycodone sustained-release tablets after opioid rotation.” The following regression equation was obtained: Y=1.736X -6.484, r ²=0.956, indicating a strong correlation. The dose-conversion ratio calculated from the regression equation was 1:1.7. This result is consistent with the dose-conversion ratios of 1:1.3 to 1:2.0 for continuous intravenous morphine:oxycodone sustained-release tablets. It is important to emphasize that the dose-conversion ratio in our study was directly calculated from actual clinical data.

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Vascular pain is a characteristic adverse effect of gemcitabine (GEM) intravenous infusion, but risk factors have not been sufficiently examined. We conducted logistic regression analysis to determine vascular pain-associated clinical factors and evaluated the protective effect of NSAIDs and opioids against GEM-induced vascular pain.Four-hundred-fifty-seven patients (total number of doses: 3,306 infusions) who received GEM therapy from April 2006 to March 2011 were analyzed. As a result of multivariate logistic analysis of patient backgrounds, administration of opioids (no) and sex (female) were independent risk factors related to the onset of vascular pain by GEM. No statistically significant difference was demonstrated, but the incidence of GEM-induced vascular pain was 29.7% in patients administered opioids compared to 38.6% in those without analgesics.These findings suggest that some prophylaxes for vascular pain are necessary from the initial dose of GEM in patients having such a risk factor.

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In order to reduce renal toxicity, hydration (2500-5000 mL) has been recommended in Japan before and after cisplatin has been administered. We planned the short hydration regimen based on the National Comprehensive Cancer Network (NCCN) Guidelines for cisplatin-based chemotherapy in patients with lung cancer. To verify the safety and tolerability of the short hydration regimen, we compared the renal functions of patients who were treated with the usual regimen(standard group) with patients treated with a short hydration regimen (short group). All subjects with lung cancer received cisplatin (≥60 mg/m²/cycle)-based chemotherapy. Twenty-eight patients received the treatment in each group. Renal function was evaluated on the first course according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0). The “Standard group” had 1 patient (3.6%) with grade 0, 22 patients (78.6%) with grade 1 and 5 patients (17.9%) with grade 2. The “Short group” had 3 patients (10.7%) with grade 0, 23 patients (82.1%) with grade 1 and 2 patients (7.1%) with grade 2. Then only 1 patient (3.6%) in the “Short group” discontinued the treatment because of renal toxicity. There was no significant difference between the “Standard group” and the “Short group” in the incidence of renal toxicity. Thirteen patients (46.4%) in the “Short group” were able to switch from hospital treatment to ambulant treatment on the second course. The results of this study indicate that not all patients with lung cancer undergoing cisplatin-based chemotherapy require the usual hydration regimen. Some patients might tolerate a short hydration regimen.

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Mitotane has been used for adrenal cancer and inoperable Cushing's syndrome. In a previous study, monitoring of the plasma mitotane level is important for assessments of efficacy and adverse drug reactions such as digestive symptoms.A simple and highly sensitive high-performance liquid chromatographic method was developed for the determination of mitotane in human plasma. Mitotane and 2,2-diphenylpropane as an internal standard were extracted from plasma with ethyl acetate. They were separated by a J'sphere ODS-H80 column with a mixture of methanol-acetonitrile-water (81:6:13, v/v/v) as a mobile phase, and were then detected with a UV detector at 210 nm. The within- and between-day variations for Mitotane were reliable. The method is very simple, rapid, sensitive and selective for mitotane, and may therefore be useful as a routine analysis for the therapeutic drug monitoring of mitotane.

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Chemotherapy-induced nausea and vomiting (CINV) reduces patient's quality of life and the intensity of treatment. Therefore, the control of CINV is necessary to enable continuation of cancer chemotherapy. Many guidelines on CINV recommend using aprepitant in chemotherapy in cases with high emetogenic risks and in some cases with moderate emetogenic risks. However, there is no report that verifies the efficacy of aprepitant intended for carboplatin with moderate emetogenic risks. We investigated the safety and effectiveness of aprepitant for the prevention of CINV based on carboplatin chemotherapy. Eighty patients with lung cancer who received high dosage (AUC5 or more) carboplatinbased chemotherapy from February 2010 to March 2011 were the subjects of the present study. The administration group was 32 patients who were also administered aprepitant and the control group was 48 patients with no administration of aprepitant. We assessed CINV, use of rescue medication and adverse events during the observation phase. The percentage of patients with no vomiting or no rescue medication at the delay phase was significantly higher in the administration group (96.9% versus 75.0% in the control group). However, the percentage of patients without nausea was not significant between groups, the percentage of patients without nausea of Grade 2 or more was significantly higher in the administration group (96.9% versus 77.1% in the control group). The adverse events were not significant between groups. These results suggest that the addition of aprepitant is useful for the prevention of CINV at the delaying phase in lung cancer patients receiving moderate emetogenic carboplatin-based chemotherapy.

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A large number of patients consult multiple healthcare institutions, use over-the-counter drugs, and consume health food. Medication notebooks are very important for them to prevent negative “drug-drug,” “drug-food,” and “drug-disease” interactions. However, it is very difficult to evaluate the effects and utility of medication notebooks in the clinical setting. In this study, we assessed their effects and utility based on changes in the numbers of questions asked at a 24-hour consultation service provided by an insurance-based dispensing pharmacy (January 2010～July 2011). We compared the usefulness of medication notebooks, no active intervention (January 2010～June 2010) and active intervention (July 2010～July 2011). Our results show that following advice on the proper use of medication notebooks provided by pharmacists for patients, there was a significant decrease in the number and the rate of questions(the number of questions 15.7 to 11.1, the rate of questions 11.5 to 8.7, p<0.05) regarding the influence exerted by a combination of drugs prescribed by multiple medical institutions and over-the-counter medicine. The results show that advice on the proper use of medication notebooks provided by pharmacists on a regular basis serves as an effective tool for reducing questions when administering more than one drug.

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