We developed a method for the analysis of anti-allergic drugs cetirizine/levocetirizine in dried breast milk spot (DMS) samples to facilitate sample transport for lactating mothers. DMS were prepared by spotting 25 - 35 µL of human breast milk on each circle of Whatman® indicating FTA® DMPK cards. The 8 mm disks from the central part of the DMS samples were punched out and extracted using acetonitrile/water. Chromatographic separation was achieved on a reverse-phase C18 column with 10 mM ammonium formate / 0.1% formic acid buffer in water/acetonitrile. Detection was by a triple quadrupole mass spectrometer equipped with a heated electrospray ionization source. The method was validated with the range 0.5 - 100 ng/mL for cetirizine and levocetirizine. Observed cetirizine and levocetirizine concentration of DMS using spiked breast milk was strongly correlated with the sample extracted from spiked breast milk. DMS using breast milk donated from cetirizine administrated patients were also correlated with the sample extracted from whole breast milk. The assay was validated over the concentration range 0.5 - 100 ng/mL. Accuracy ranged within 15% and precision did not exceed 15％. The average recovery of cetirizine and levocetirizine from DMS was 86.1% and 84.9%, respectively. Stability in DMS at room temperature, 4℃ and -20℃ for 14 days was demonstrated. The validated method, proved stability in DMS and the correlation study showed the capability of the DMS method to be used as a mode of transport for breast milk in a clinical study about drug transfer to breast milk.
Afatinib is an irreversible oral ErbB family blocker. It demonstrates a side-effect profile similar to that by the first-generation epidermal growth factor receptor-tyrosine kinase inhibitor, with diarrhea being the most frequently reported adverse event (AE). Moderate and severe diarrhea can have a significant effect on patients' quality of life (QOL).
In this study, we retrospectively investigated the medical records of 66 afatinib-treated patients between May 2014 and December 2015, aiming to identify the risk factors for associated diarrhea.
Multivariate logistic regression analysis showed that being female (odds ratio = 5.370, 95% CI = 1.050-27.50, P = 0.044) and abnormal stool hardness (loose or hard) (odds ratio = 4.820, 95% CI = 1.170-19.90, P = 0.030) were significant risks for moderate to severe diarrhea associated with afatinib. Thus, we identified the risk factors for afatinib-associated diarrhea at the start of afatinib administration. This provides useful knowledge on managing the side effect and helps maintain patients' QOL. Furthermore, we showed the necessity of checking the condition of patients' stool prior to afatinib administration.
We previously reported that insoluble particulate matter formed during the mixing of injectable drugs. We considered that the contamination derived from the disposable injection syringe used for the mixture as one of the causes. Therefore, in the present study, we evaluated the amount of insoluble particulate matter caused by using a 50-mL syringe of each manufacturer, using syringes of various capacities and number of piston times (suction and expulsion) of the syringe. Furthermore, we were able to identify the components of the insoluble particulate matter that formed. As a result, we found that a lot of insoluble particulate matter was expelled from the 50-mL syringes of each manufacturer that increased with the capacity of the syringe and the number of piston times. In addition, we found that the insoluble particulate matter was from the silicone oil coating on the inner surfaces of the syringes.
We investigated rubella antibody titer during pregnancy, delivery history, and labor age in 728 pregnant women between January 2013 and December 2013 in Kobe City Medical Center General Hospital. Among 728 pregnant women, women with high antibody titer numbered 534, and women with low antibody titer numbered 194. In total, the rubella antibody prevalence rate in this study was 73.4% and the percentage of pregnant women with low antibody titer was 26.6%. The rubella antibody prevalence rate of 387 primiparous and 341 multiparous women was 72.4% (280) and 74.5% (254), respectively. Their delivery histories were not related to the rubella antibody prevalence rate (P = 0.52), but pregnant women with high antibody titer were significantly older than pregnant women with low antibody titer (P = 0.0002). We started to recommend receiving the post-partum rubella vaccine to 157 pregnant women with low antibody titer from February 2013. One hundred and thirty-six (86.6%) pregnant women with low antibody titer received the postpartum rubella vaccine according to our recommendation. One of the effective measures to prevent future occurrences of Congenital Rubella Syndrome is to aggressively recommend rubella vaccination so that pregnant women with low antibody titer do not miss an opportunity to receive the post-partum vaccination.
At the University of Tokyo hospital, we began allocation of ward pharmacists to some wards in August 2012 and to all wards in August 2014. In this study, we qualitatively and quantitatively reviewed cases reported by ward pharmacists to evaluate the effects of this allocation on intervention and consultation that required positive participation.
We retrospectively reviewed the pharmaceutical interventions' record from April 2012 through March 2015. We also analyzed cases for three months after the allocation of pharmacists to every ward. We found a highly positive correlation (R2 = 0.928, P < 0.0001) between the number of wards and pharmaceutical interventions. Intervention cases per month increased by 21.5 after allocating a pharmacist to a ward. There were a total of 2,438 intervention cases over three months. Active and passive approaches were employed in 1,833 cases and 605 cases, respectively. High-risk medicines were associated with 39.3% of cases. The prescription change rate was 86.2% for active interventions and 50.9% for passive interventions.
Results showed that the allocation of a ward pharmacist could assist pharmaceutical approaches through the evaluation of patient complaints and clinical conditions, participation in the treatment plan, and consultation from medical staff. There were also reports that an active approach led to critical adverse event avoidance and pharmacotherapy effect improvement. These findings suggest that the allocation of ward pharmacists results in the promotion of healthcare services and medical safety.
Recently, the intake of health foods has been steadily increasing, in order to preserve health, and to cure and/or protect from diseases. At the same time, a noticeable increase in adverse drug reactions caused by health foods has been reported. Cytochrome P450 is a family of enzymes responsible for the metabolism of a wide variety of xenobiotics, including therapeutic agents and environmental chemicals. In this study, we investigated the effect of health foods on metabolism by using cultured cells expressing CYP1A1 and CYP1A2 gene reporters. Expressed CYP1A1 and CYP1A2 catalyze not only detoxification and activation of carcinogens but also the metabolism of drugs such as phenacetin and theophylline. Among 175 health food extracts examined, 20 extracts increased the CYP1A1 gene reporter activity, especially extracts of St John's wort, turmeric-containing health foods, garlic-containing health foods, and vitamin/mineral-containing health foods. In addition, these health foods increased CYP1A1 and CYP1A2 mRNA expression in HepG2 cells and human cryopreserved hepatocytes. These results indicate that health food-drug interactions might be mediated through CYP1A2 activities.
The National Action Plan on Antimicrobial Resistance was implemented by the Ministry of Health, Labor and Welfare in Japan in 2016. The aim is to reduce the use of broad spectrum antibacterial drugs and optimize the use of oral antimicrobials. Ogaki Municipal Hospital has been promoting the use of cephalexin (CEX) and the combination of amoxicillin and clavulanate potassium (AMPC/CVA) since these drugs were added to the drug formulary in December 2012. In this study, we compared trends in oral antibiotic use in the emergency department before and after the addition of CEX and AMPC/CVA to the formulary. We observed a significant decrease in the average monthly consumption of third-generation cephalosporins (before: 264.3 ± 58.2 days; after: 108.5 ± 35.2 days; P < 0.01), and of macrolides (before: 52.7 ± 21.9 days; after: 18.9 ± 13.7 days; P < 0.01). Cost savings on oral antibiotics following the formulary revisions were calculated as 500,000 yen over three years. No difference in clinical effect was observed when comparing CEX, AMPC/CVA, and a third-generation cephalosporin. Therefore, we recommended the use of CEX and AMPC/CVA, according to the hospital formulary, in order to change trends in oral antibiotic use and achieve the objectives of the National Action Plan on Antimicrobial Resistance.