The Japanese Society for Palliative Medicine has published a Clinical Practice Guideline for cancer pain management. In this Guideline, high-dose acetaminophen (2.4-4.0 g/day) is recommended to treat cancer pain. However, the effect of acetaminophen at different high doses on cancer patients has not been reported in Japan. This study was conducted to retrospectively investigate the effects of different high doses of acetaminophen on patients with cancer pain who were treated, as well as on the hepatic toxicity. Patients were divided into three groups who received acetaminophen at 2.4 g/day (n = 45), 3.2 g/day (n = 46), and 4.0 g/day (n = 20), respectively. Pain was scored according to the numeric rating scale (NRS). No significant differences were observed between the 2.4 g group, 3.2 g group and 4.0 g group regarding the incidence of Grade 2/3 hepatic toxicity (4.4％ vs 4.3％ vs 5.0％, respectively; P = 0.993). In contrast, significant differences in the NRS score were observed before and after acetaminophen administration in the 3.2 g group (n = 18) and 4.0 g group (n = 9), but not in the 2.4 g group (n = 16). The mean difference in the NRS score was 2.11 (P = 0.001) in the 3.2 g group, 1.56 (P = 0.028) in the 4.0 g group, and 0.44 (P = 0.297) in the 2.4 g group, respectively. In this research, acetaminophen administration at the dose of 3.2, 4.0 g a day was effective for the treatment of cancer pain.
Many biosimilars have been launched recently, however, a precise analytical method to evaluate their characteristics has not been developed. In this study, we established a new qualitative analysis technology for biomedicines using liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (LC/QTOF-MS), and assessed the original product and 4 biosimilars of filgrastim. Three peaks (Peak 1-3) appeared in total ion chromatogram by LC/QTOF-MS in the original brand-named drug. Filgrastim appeared as the main peak (Peak 1), and its molecular weight was calculated to be 18798.96 ± 0.02. When the original product was reduced by dithiothreitol, the molecular weight was 18802.19 ± 0.47, which was identical to the theoretical value based on amino acid sequence. These results indicate that it is possible to measure and distinguish molecular weights of untreated and reduced forms of filgrastim by LC/QTOF-MS. In addition, main peaks from all products including biosimilars showed exactly the same mass spectra and calculated molecular weights, suggesting that the main components (filgrastim) in these 4 products were considered to be qualitatively equal. On the other hand, the area ratios of 2 secondary peaks (Peaks 2 and 3) against the main peak (Peak 1) in 2 biosimilars were higher than those in the original product. The calculated molecular weights in Peaks 2 and 3 corresponded to that of polysorbate 80, which was one of the additives in the formulation. In conclusion, LC/QTOF-MS is a useful technique for qualitative component analysis of biomedicines.
The pharmaceutical service for outpatients with asthma has been provided by hospital pharmacists in Asahikawa Medical University Hospital since 2007. In the service, the patients who require pharmaceutical interventions are being educated on asthma management and inhaler techniques. This retrospective study is aimed at verifying the effectiveness of providing multiple pharmacist-led patient education on asthma control. The asthma control test (ACT) scores during the first four visits were assessed. Of the 128 outpatients with asthma who received this service between February 2007 and May 2013, 51 patients who visited at least twice were included in this study. The ACT scores were significantly increased at the second, third and fourth visit as compared with the first visit (P < 0.05). Furthermore, significant improvement in the ACT score was achieved in the case of a visiting interval shorter than eight weeks (P < 0.05), whereas no significant improvement was observed in the case of an interval of eight weeks or longer. These results demonstrate that the continuous pharmacist-led patient education over multiple sessions was effective in improving patients’ asthma control.
Palatability plays a significant role in treatment compliance, notably in children. Poor compliance increases the risk of therapeutic failure. The European Medicines Agency considers it desirable that the acceptability of oral medicines for pediatric patients is evaluated by target age group based on the Guideline on the pharmaceutical development of medicines for paediatric use. However, the palatability test of the pediatric population is concerned about the lack of versatility, robustness and repeatability. In this study, we evaluated the palatability of sour syrups as a corrigent in children aged 3 to 6 years old. The repeatability and acceptability were tested in 50 children using 6 test drugs (25％ or 50％ simple syrup solutions, dilute hydrochloric acid solution with 25％ or 50％ simple syrup and citric acid solutions with 25％ or 50％ simple syrup solutions). The repeatability was evaluated by the correlation of the palatability score in two tests on different days. The palatability assessment was based on a 5-point scale, according to a method in a previous study by Popper R et al. As a result of the repeatability test, the palatability scores of all 6 syrups revealed a correlation (correlation coefficient (r) > 0.75). In the 4 sour syrups, a greater preference was shown for dilute hydrochloric acid solutions with simple syrups than for the citric acid solution with simple syrups. These results suggest that the syrup containing citric acid might cause avoidance. Sour syrup including citric acid and syrup have the effect of suppressing bitterness, so an acceptability test of the mixture of the drug and sour syrup is required.
We retrospectively evaluated the effects of intravenous azithromycin (AZM) in 76 elderly patients (mean age, 72.8 y) with pneumonia based on Nursing and Healthcare-associated pneumonia (NHCAP) guidelines for a mean of 5 days between April 2012 and March 2013.
Those who met the NHCAP guidelines (NHCAP; n = 30) were significantly older than those with community-acquired pneumonia (CAP; n = 46) (82.7 vs. 66.3 years, P < 0.05), and had higher A-DROP scores. The NHCAP group was distributed among inpatients categories B to D in the NHCAP guidelines. The ratio of patients with anti-Pseudomonas aeruginosa activity treated with a combination of antibiotics was higher among the NHCAP, than the CAP group (P = 0.02). We excluded 13 patients with missing AZM data and then 22 of 52 among the remaining 63 patients for whom AZM was effective, continued therapy with concomitant antibiotics. Among 11 patients for whom AZM was ineffective, one died and nine were switched to fluoroquinolones. Azithromycin significantly reduced the levels of C-reactive protein, whiteblood cell and neutrophil counts in the patients for whom AZM was effective (all P < 0.05).
Pharmaceutical care approach to clinical AZM administration could extend understanding of the phamacotherapy of infectious diseases among pharmacists.
Studies in rabbits have been performed to evaluate the intraocular pressure (IOP)-reducing effect of various anti-glaucoma eye drops and eye drops of latanoprost (LP), which is a selective agonist of prostaglandin F receptor (FP). However, the sensitivity and localization of FP receptors in the rabbit eye are different from those in humans, and studying the relationship between IOP regulation and FP receptors in rabbits is important for the evaluation of antiglaucoma eye drops. In this study, we investigated whether stimulation of FP receptors in rabbits affects the regulation of aqueous humour production via β receptors by using the LP and the β-blocker timolol (TM). Ocular hypertension was induced in the rabbits by the infusion of a 5％ glucose solution (15 mL/kg). Although no reduction in IOP was observed after the instillation of saline and 0.005％ LP, 0.5％ TM eye drops significantly reduced IOP. The IOP-reducing effect, as measured by area under the curve (AUC∆IOP) in rabbits treated with TM eye drops, was 81.3％ that of LP 0.005％/TM 0.5％ fixed combination (LTFC) eye drops, and the TM concentration in the aqueous humour following the instillation of LTFC eye drops was similar to that of TM eye drops. These results show that the stimulation of FP receptors affects the production of aqueous humour via β receptors in rabbits, meaning the rabbit model is not suitable for the evaluation of anti-glaucoma eye drops with FP receptor activity, since this drug effect was not observed in humans.
Many generic products of latanoprost ophthalmic solution are commercially available. For pharmacists' guidance, patients often ask questions, such as the total number of drops to be used per bottle. However, materials, including package inserts, that can be obtained from pharmaceutical companies do not provide such information, such as the total number of drops, the volume of a drop, or sense of use regarding each preparation. In this study, we compared the total number of drops, the weight of a drop, squeezing force, and sense of use using brand-name and generic products of latanoprost ophthalmic solution to establish selection criteria.
The weight of a drop exceeded 25 mg in all products, but there were significant differences among the products. In generic products, the total number of drops per bottle was lower than in the brand-name product (112.6 ± 0.9 drops), showing significant differences (10 to 20 drops). The squeezing force required for dripping differed among the products (1.5 to 5-fold). The sense-of-use score regarding the rigidity of an eye drop container reduced with the increase in the squeezing force, showing a negative correlation. The utilization of this information may improve glaucoma patients' adherence and/or reduce costs, providing beneficial information for adopting pharmaceutical preparations in medical institutions.