The renal clearance of carboplatin, which is a second-generation platinum compound, is correlated with the glomerular filtration rate (GFR). As the area under the concentration-time curve (AUC) of free carboplatin is related with efficacy and toxicity following carboplatin administration, carboplatin dosing is defined as a target AUC and generally calculated by the Calvert formula according to the patient's GFR. We conducted a survey on the usage of the Calvert formula to clarify the current situation in Japan. As a result, the value of creatinine clearance (CLcr), which is higher than GFR due to the tubular secretion of creatinine, has been used as a substitute for GFR for the Calvert formula without appropriate correction in 71 of 109 institutions, where CLcr estimated by a Cockcroft-Gault equation and/or obtained by 24-h urinary collection are used. On the other hand, body surface area-indexed values of renal function have been directly used without conversion to individual values in 42 of 71 institutions, where GFR estimated by a Japanese equation and/or CLcr estimated by a Jelliffe equation are used. It was found that the desired dosing of carboplatin has not been administered to patients in a number of institutions. Back to the original concept of the Calvert formula, it is reasonable to use a GFR estimated by the Japanese equation and converted to an individual value. In addition, we need to assess tolerability following carboplatin administration and discuss the appropriateness of the starting dose for each patient without being overly reliant on the dose obtained by the Calvert formula.

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The combination of 5-HT₃ antagonist (5-HT₃) with dexamethasone (DEX) and aprepitant (AP) is recommended for preventing vomiting when undergoing highly emetogenic chemotherapy including cisplatin (CDDP). Little is known about the efficacy of antiemetic therapy and risk factors on vomiting after hepatic arterial chemotherapy with CDDP. We carried out a retrospective cohort study to analyze the risk factors and preventive effect of antiemetics for vomiting in 77 patients who received therapy with CDDP suspension in lipiodol (CDDP・LIP) for hepatocellular carcinoma for the first time at Mie University Hospital between January 2009 and October 2014. Ten (13%) and 7 (9%) patients developed vomiting in acute and delayed phases, respectively. In the overall period (acute and delayed phases), the complete response for vomiting (100%) in patients with 5-HT₃, DEX, and AP was significantly higher than that (65%) in patients with 5-HT₃ alone (P = 0.024). Multivariate logistic regression analyses showed that the single administration of 5-HT₃ in the acute phase (odds ratio (OR): 4.748, P = 0.037) as well as female gender (OR: 9.439, P = 0.047) and dose of LIP (OR 1.051, P = 0.029) in the delayed phase were considered to be risk factors of vomiting. These results suggest that a combination antiemetic therapy using 5-HT₃ with DEX and AP should be recommended in patients with the above risk factors of vomiting after CDDP・LIP therapy. The present findings provide useful information for the achievement of effective antiemetic therapy to improve the quality of life in patients receiving CDDP・LIP therapy for hepatocellular carcinoma.

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In the perioperative period, some medicines used have a high-risk of causing serious medical accidents. With the reform of healthcare, the number of cases of surgery managed by anesthesiologists is increasing year by year. Therefore it is expected that pharmacists will contribute to medical care more for the perioperative period. In St Luke's International Hospital, pharmacists started duties in the operating room in April 2013. We investigated pharmacists' duties and examined the effects of the skill mixture of the perioperative care team. The main medicines prepared by perioperative pharmacists were vasopressors, intravenous anesthetics, muscle relaxants and narcotics used in the operations that anesthesiologists managed. The ratio of preparation medicines by perioperative pharmacists was 81.3% of scheduled operations. After pharmacists started duties in the operating room, time of work associated with medicines decreased by 5.35 minutes per surgery. The interval time between surgeries shortened by 14.6 minutes and the ratio of entering the operating room on schedule increased by 3.2%. These findings suggest that the skill mixture of perioperative pharmacists contributed to perioperative time management and efficiency of the operation administration and contributed also to hospital management. It is important to investigate the clinical significance of perioperative pharmacists' duties in terms of the perioperative medical quality and safety.

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We investigated whether the component in cataplasm transmitted into hemorrhoid ointment in the combined storage of hemorrhoid ointment and non-steroidal anti-inflammatory drugs (NSAIDs) cataplasm. The NSAIDs cataplasm was used as a commercially available methyl salicylate (MS reishippu “TAIHO”, MS cataplasm) and indomethacin (Catlep^®, IMC cataplasm) cataplasm. In addition, the hemorrhoid ointment was in a polyethylene container with (Neriproct^® ointment, DFV-L ointment) or without aluminum laminate (Posterisan^® forte, HC ointment). As for the methyl salicylate, 5.68 mg / pieces in HC ointment were detected at 40 weeks of combined storage with MS cataplasm. The methyl salicylate concentration in DFV-L ointment was lower than that in HC ointment under the same conditions. On the other hand, no contamination of indomethacin in HC and DFV-L ointment was observed in the combined storage with IMC cataplasm. These results show that the methyl salicylate in cataplasm passed the polyethylene container, and provide significant information on the risk of contamination by the combined storage of cataplasm and hemorrhoid ointment.

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The pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence between the filgrastim biosimilar “Mochida” and filgrastim have been confirmed in clinical pharmacology studies in healthy volunteers. In a phase III breast cancer clinical trial, patients were administered FEC therapy (fluorouracil, epirubicin, cyclophosphamide), but a comparison with filgrastim was not performed. Therefore, we conducted a prospective, randomized crossover comparative study of “Mochida” and filgrastim. The results of this study showed no significant difference in the mean duration of neutropenia, incidence of febrile neutropenia (FN), incidence of absolute neutrophil count (ANC) less than 1000, and mean duration of ANC nadir between the two drugs. Although there were only 16 patients in this study, “Mochida” showed no significant difference with filgrastim for efficacy, and it was suggested that “Mochida” is an effective drug for avoiding FN expression after chemotherapy. In addition, “Mochida” costs 54%-69% of the price for filgrastim. Thus, “Mochida” may contribute to maintaining quality of life.

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The package insert of notandum, a narcotic drug, states that patients who take this drug must not drive a car, or should drive a car carefully. Many drugs used in supportive cancer chemotherapy and palliative therapy contain warnings regarding driving a car. Twenty-one of 127 outpatients in our hospital who received cancer chemotherapy were prescribed drugs that affect car driving. Sixteen patients drove a car on a daily basis. Although patients would receive a warning from their physician or pharmacist regarding driving when prescribed narcotic drugs, repeated warnings should be given, and driving status should be checked. Fourteen patients stated that refraining from driving was difficult. Therefore, pharmacists proposed prescribing drugs that do not affect driving to these patients. By changing their therapeutics to anti-emetics and supplementary analgesics, the patients could drive without worsening their condition. When selecting drugs, the necessity of driving should be checked to maintain quality-of-life. Nevertheless, as all patients who take opioid analgesics in palliative therapy must refrain from driving, and as opioid analgesics cannot be replaced with other drugs, it is necessary to check the validity of the descriptions in the package insert in future.

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The BD Phaseal^TM administration set, a new device for the BD Phaseal^TM closed system drug transfer device (CSTD), can prevent the occupational exposure of health caregivers to antineoplastic agents during all stages of the treatment process from preparation to administration. Further, a revised nursing approach for administration may prevent inadvertent antineoplastic agent spills. In this study, we compared the exposure levels of cyclophosphamide (CPA) and paclitaxel (PTX) between conventional methods and the new method described above; by sampling drug absorption sheets (a sampling sheet method) was used. In both methods, CPA was prepared using the BD Phaseal^TM CSTD and PTX was a plastic needle open system. For the new method, CPA was administered using the BD Phaseal^TM administration set and PTX was the revised nursing administration approach. Five pharmacists undertook the preparation process, and five nurses the administration process. Within the administration process using the conventional method, the following levels were detected: CPA 1.67 ng/cm² and PTX 0.077 ng/cm². No measurable levels were detected with the new method. For the preparation process, no CPA was detected, but PTX was detected. These results suggest that the use of the BD Phaseal^TM administration sets and the revised nursing administration approach is useful for preventing the occupational exposure of health caregivers to antineoplastic agents; this applies to both the preparation process and the administration processes.

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This study investigated the influence of treatment with statins on the effect of sitagliptin in obese patients with diabetes.
We studied 52 patients with type 2 obese diabetes who were started on sitagliptin from April 1, 2010 to March 31, 2012. Of these patients, 31 were taking a statin and 21 were not. HbA1c levels were measured at 0 and 3, 6, and 9 months after initiation of sitagliptin.
In obese patients (BMI ≧ 25 kg/m²), a significant improvement in HbA1c levels was observed only in those taking statins.
Our findings suggest that statins may modify the glucose-lowering effect of sitagliptin in obese patients with type 2 diabetes.

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