The hepatitis B virus (HBV) is a serious concern for people at high risk of exposure to blood in their work because it is very infectious. While infection can be prevented by acquiring antibodies from hepatitis B vaccine, there are low responders and non-responders to the vaccine. We examined 2 possible methods of overcoming this problem: performing an additional vaccination with a different type of vaccine and carrying out 2 additional vaccinations at monthly intervals. Regarding the former method, an additional vaccination with a different vaccine type was carried out for a subject who could acquire no antibodies after undergoing 2 series of 6 vaccinations and who had not had any antibodies to hepatitis B for about 10 years. One month later, the passive hemagglutination test (PHA test) showed that the subject had obtained a 512-fold increase in the number of antibodies. As for the latter method, 3 of 5 non-responders acquired antibodies. Also, 5 of 6 subjects who were less responsive to the vaccine acquired antibodies and maintained them for at least 3 years. We intend to improve immunization coverage by using the methods examined in this study.
It is necessary to pay attention to drug interactions that influence the pharmacokinetics of anticancer drugs used for chemotherapy because the therapeutic window of such drugs is narrow. However, very few studies have been done on potential interactions with anticancer drugs used for chemotherapy. We therefore analyzed information on drug interactions among patients undergoing cancer chemotherapy at JA Aichi Kouseiren Atsumi Hospital. More than half of the registered chemotherapy regimens included anticancer agents that have contraindicated drugs and all of the regimens included anticancer agents that have significant drug interactions. Logisticregression analysis showed that the risks of “unintended drug interactions”, drug interactions other than those due to additive or synergistic effects expected from the combination of drugs administered for cancer chemotherapy and palliative care therapy, were enhanced by increases in the numbers of concomitant drugs and drugs prescribed by other clinics being taken by patients. In conclusion, there are a large number of potential drug interactions in cancer chemotherapy and many are clinically important. Our findings indicate that attention should be paid to unintended drug interactions with regimens that include diphenhydramine or anticancer drugs that are metabolized by cytochrome P450 (CYP), as well as when antihypertensive drugs, antidiabetic drugs or central nervous system suppressants are being taken concomitantly.
Recomodulin® Inj. 12800 is an injectable form of thrombomodulin alfa, the extracellular domain of human thrombomodulin that includes the active site. It is produced as a soluble molecule in CHO cells by recombinant techniques. Thrombomodulin alfa is a novel therapeutic for disseminated intravascular coagulation (DIC) with a mechanism of action completely unlike those of existing drugs. It is conveniently administered by intravenous infusion for 30 min once daily via a peripheral vein. However, since adsorption on to lines and filters of infusion sets and other medical equipment is a problem with protein formulations such as insulin and G-CSF, we performed adsorption testing on 12 commonly used commercial infusion sets with the aim of assessing the adsorption of thrombomodulin alfa in such sets. The lines of the infusion sets were made of 2 different materials, polyvinyl chloride and polybutadiene, and filters of 3 different materials, polyethersulfone, polysulfone and nylon 66. The recovery rates of thrombomodulin alfa from the infusion sets were 92-107%. Such very low levels of adsorption indicate that thrombomodulin alfa can be administered without concern over adsorption-related decreases in the amount of drug delivered.
We have developed a photocatalytic agent (CHEMOCLEAN) containing TiO2 solution and examined its degradation of residual cyclophosphamide (CPA) in a biological safety cabinet (BSC). In this study, the degradation effects of the photocatalyst on various other anticancer drugs were also investigated. A certain concentration of each anticancer drug (CPA, 5-Fluorouracil; 5-FU, Methotrexate; MTX, Paclitaxel; PTX, Iirinotecan; CPT-11) was placed on 100-cm2 stainless plates, and the photocatalytic agent was sprayed at 150 g/m2. Then, the plates were irradiated with near-ultraviolet (wavelength: 350 nm) radiation in the BSC for 12h. The residual drugs were extracted from a paper used to wipe the plates and their concentrations measured using high-performance liquid chromatography. We found that the degradation rate of the anticancer drugs tended to increase with reduction of the loading dose. The photocatalytic solution degraded CPA(50 μg), 5-FU(100 μg), MTX(100 μg), PTX(50 μg), and CPT-11(100 μg)by 78%, 86%, 97%, >99% (below quantification limit), and 87%, respectively. From these results, we conclude that the degradation effect of the photocatalytic agent appears to be similar for every anticancer drug, and that it will be useful for reducing the concentrations of residual anticancer drugs.
The report of the Japan Council for Quality Health Care in 2009 shows that 26.4% of medical incidents were related to medication. In Japan, not pharmacists but ward nursing staff are mostly responsible for pharmacy tasks at present, and the involvement of pharmacists in such tasks is expected to improve medical security. Recently, the concept of ‘skill mix’, meaning bringing together the skills of various healthcare professionals in hospital medical teams, has been attracting attention. In order to clarify the expectations and needs of the professionals involved, we conducted a survey of 175 nurses, 29 pharmacists and 50 doctors. The collection rates of the completed survey from the nurses, pharmacists and doctors were 74.3%, 93.1% and 94% respectively. Many nurses were concerned about their knowledge of drugs, and they also felt that their performance of pharmacy tasks negatively affected the nursing services they provided. Nurses and doctors hoped that pharmacists could be present in wards and participate in pharmacy tasks. In particular, nurses hoped that they would carry out the mixing of injection drugs, preparation of premixed injection drugs and preparation of oral medicines. They also tended to want pharmacists to carry out pharmacy tasks which required neither close communication with patients nor special knowledge of diseases. However, nurses who worked with pharmacists constantly in the ward wanted them to participate in many kinds of pharmacy task which required close communication with patients.
A nondestructive analysis technique using Raman spectroscopy was developed to measure the concentrations of the components of admixed injectable drugs. Taking Gaster® injection as the model injectable drug, several Gaster® saline solutions of clinical doses were prepared and put in plastic saline bottles and polypropylene syringes. The Raman spectra of Gaster® injection had sharp peaks at around 1045 cm−1. These peaks coincided with that of nicotinamide, which was present at a fixed concentration of 50 mg/mL in the solutions. When Gaster® injection was prepared in a quartz cell (to exclude effects due to the plastic bottles and polypropylene syringes), the peak area from 1025 to 1056 cm−1 was well correlated with that of the content of the injection. Further, based on Raman measurements from the surface of the plastic bottles and the polypropylene syringes, there was a linear relationship between the nicotinamide concentration and the peak area from 1025 to 1056 cm−1, that is, in this area there was no overlapping of peaks. These results indicate that Raman spectroscopy can be used for the nondestructive densitometry of the component concentration of an injectable drug after its preparation.
Contamination by cytotoxic drugs has been discovered in Japanese hospitals through the wipe test on cyclophosphamide (CPA). Previously, such contamination testing was mainly entrusted to laboratories in other countries but KOBELCO RESEARCH INSTITUTE (Lab-K) has begun to analyze for CPA contamination by means of the wipe test as a commercial operation using LC/MS/MS. We conducted a comprehensive evaluation of the equivalence of analysis performed by an official Japanese testing laboratory (Lab-O) and Lab-K. Diluted Sample  (CPA 34.4 ng/0.15 mL) or Sample  (CPA 103.2 ng/0.45 mL) were accurately prepared and used for the wipe test. From the analysis data produced by each laboratory, error rates and variation coefficients were calculated, and from them the accuracies and true rates obtained, having within 15% as the target range. The time taken for the analyses, their costs and other details were also checked. The results of the analyses (expressed as LabO/LabK) were:  37.7 +/- 5.0/31.7 +/- 1.5 ng and  93.7 +/- 3.8/89.3 +/- 9.1 ng, respectively. The respective error rates and variation coefficients were within the target range. Based on this, we considered that LC/MS/MS did not differ from other analysis techniques in terms of sensitivity with respect to wipe samples of CPA from the environment. However, the target drug of the wipe test in LabK was only CPA and it was not measured in urine. In the future, the wipe test should be extended to other drugs and urine samples analyzed for their contents as well.