Vancomycin is mainly eliminated via the kidneys and has a narrow therapeutic range.High doses of vancomycin cause nephrotoxicity,particularly if it is used in combination with aminoglycoside antibiotics.The area under blood concentrationtime curve (AUC)/minimum inhibitory concentration (MIC) is the pharmacokinetic/pharmacodynamic (PK/PD) parameter that best correlates with a successful outcome for vancomycin.Therefore,the appropriate setting of initial doses is important to vancomycin therapy and pharmacists should actively design effective initial dose settings for the drug. In initial dose setting with a nomogram using serum creatinine concentrations,serum vancomycin trough concentrations cannot be accurately predicted,particularly in elderly patients.This is probably because the use of the serum creatinine concentration as a marker of renal function leads to overestimation of the glomerular filtration rate (GFR).However,it has been reported that the serum cystatin C concentration is a better marker of renal function and recent studies have shown that the serum cystatin C concentration is a better marker of the clearance of drugs eliminated by the kidneys. In this review,we focus on the usefulness of setting initial doses of vancomycin and the problems with this.We also review recent developments in the application of setting initial doses of vancomycin using the serum cystatin C concentration.
We investigated the preparation of orally disintegrating tablets (ODTs) using furosemide (FU) as a model drug.Preparations were made from granules containing 2 correctives,maltitol (MA) and yogurt powder (YO),in various mixing ratios formed by the wet granulation method,and the taste of each one was evaluated.Though all of the FU preparations had an improved taste,the mixing ratio of MA did not affect the masking effect.It appeared that a sufficient masking effect could be obtained with mixing ratio of YO/MA/FU=0.5/0.5/1 by weight. The taste masked FU tablets were prepared using the direct compression method,and microcrystalline cellulose (Avicel® PH-30citation=2)and mannitol were added as excipients at a mixing ratio of 1/1 by weight.For all formulations,the hardness of tablets exceeded 4.5 kgf.The disintegration time and water absorption time increased as the proportions of YO and MA increased.Tablets made from granules with the mixing ratio YO/MA/FU=0.5/0.5/1 exhibited the greatest hardness (above 6.0 kgf),the shortest disintegration time (within 30 sec) and the shortest water absorption time (about 100 sec).Increasing the compression force had little effect on tablet hardness but increased the disintegration time,though it did not go over 60 sec,and also increased the water absorption time. In conclusion,we found that well taste masked ODTs can be prepared with granules produced by the wet granulation method at a mixing ratio of YO/MA/FU=0.5/0.5/1 by weight.
This study examined the clinical features and risk factors of autonomic neuropathy induced by the administration of bortezomib at Social Insurance Kyoto Hospital,as well as details of an association between bortezomib and onset of autonomic neuropathy.Eleven of 32 patients (34.4%) with bortezomib-treated relapsed multiple myeloma developed autonomic neuropathy.Instances of autonomic neuropathy of more than grade 2 comprised 4 cases of paralytic ileus,1 case of hypotension,and 1 case of urinary retention.They occurred for a median of 2.5 cycles[range : 1-4],and the median cumulative dose to onset was 9.5 mg/m2[range : 3.9-18.2]. In 2 patients who continued to receive bortezomib at the same doses,autonomic neuropathy developed again but in 3 patients whose dose of bortezomib was reduced,autonomic neuropathy did not recur.In addition,the onset of autonomic neuropathy was significantly higher in patients with diseases of the autonomic nervous system and those also receiving drugs affecting the autonomic nervous system. Therefore,we were able to clarify an association between the administration of bortezomib and onset of autonomic neuropathy and our findings suggested that the risk factors for bortezomib-induced autonomic neuropathy were those affecting the autonomic nervous system.
Pharmacists working in the intensive care unit (ICU) of Saiseikai Yokohamashi Tobu Hospital are mainly responsible for managing drug stocks,providing drug information to other medical staff,educating them on rational drug therapy,and providing pharmaceutical care to patients.Based on rates of inappropriate prescriptions,those that pharmacists should make inquiries to doctors about,we retrospectively investigated the contribution of pharmacists in this respect between before and after they started working in the ICU,and made a comparison.In addition,we evaluated whether pharmacists contribute to optimizing prescriptions and medical safety management. To do this,a pharmacist in the ICU checked 4,073 prescriptions for injections issued for the 4 months before pharmacists joined the ICU team and 5,150 prescriptions issued for the 4 months after they joined it.For the former,6.41% of prescriptions required inquiries to be made whereas 1.90% of those for the latter needed inquiries,which amounted to a significant decrease in the pharmacist inquiry rate of 70.3%.We also compared problems with prescriptions before and after pharmacists’joined the ICU.After pharmacists started working there,there were significant decreases in the rates for prescription problems such as inappropriate dosage,injection speed,injection incompatibility,and administration dosage form,of 88.4 %,77.7%,91.4% and 42.3%,respectively. Our findings suggested that having pharmacists in the ICU contributes to optimizing prescriptions and enhancing medical safety.
There has been no detailed evaluation of preventive measures against exposure to oral powdered preparations of antineoplastic drugs during dispensation.In this study,we examined the effectiveness of using a dust collector in the drug dispensing environment with respect to drug dispersal as well as other contamination-related factors.Preparations of lactose powder,fine lactose granules and busulfan powder containing fluorescein sodium at 0.05 w/w% were made,and the pressure gradient of the dust collector on the powder dispensation table was set at 150,60,20,and 0 Pa.After weighing the preparations,under UV irradiation,fluorescence spots were observed on the dispensation table and masks for all pressure gradients,indicating that exposure is unavoidable.At 150 Pa,there were significantly more fluorescence spots of lactose powder on the dispensation table at 150 Pa than at 20 or 60 Pa.Also,for lactose granules,there were high concentrations of fluorescence spots in particular areas for lactose,indicating that this was an undesirable pressure gradient under which exposure was high.Fluorescence spots were also detected on powder bottles and gloves,indicating the possibility of secondary contamination and importance of cleaning immediately after weighing.The order of dispersion amounts was : lactose granules>busulfan>lactose powder,so lactose granules were considered undesirable for the dosage form of antineoplastic drugs.Regarding dispersal patterns,there were large numbers of fluorescence spots in areas closer to the dispenser at 0 Pa,and also concentrations of them in distant areas,so dispenser exposure was considered to be higher at 0 Pa.These results suggest that dispenser exposure to powdered antineoplastic drugs due to dispersion can be reduced by running the dust collector on the dispensation table at a low to medium power level.
Warfarin is medicine whose dosage is determined by measuring the prothrombin time international normalized ratio (PTINR) as an index of anticoagulant activity because of its interactions with other medicines and the large inter-individual variability in its anticoagulant effect. We report a case in which unexpected PT-INR elevation was observed after chemotherapy that included docetaxel.The patient had been administered warfarin after aorta valve substitution due to valvular heart disease and then developed ovarian cancer.An interaction between warfarin and docetaxel was suspected because PT-INR was elevated within a few days of each chemotherapy session. In addition,we examined other patients who had been on both warfarin therapy and chemotherapy including docetaxel from August 2004 to December 2009.In these patients,the warfarin sensitivity index (WSI) was elevated significantly from its baseline value of 0.48.to 0.89 after chemotherapy.It is still uncertain whether there is a definite interaction between warfarin and docetaxel and no detailed mechanism for one has yet been reported.Nevertheless,it is necessary to assume the possibility of PT-INR elevation and to monitor PT-INR frequently in managing patients on both warfarin and chemotherapy.
We developed videos and a pharmacist simulator as methods of instructing students in medical communication in the pharmaceutical education curriculum.The videos consist of a model edition (4-5 minutes) and a commentary (6-10 minutes).There are 3 instances of initial interviews with patients and 5 instances of providing information to them.Students can view them on the website of Gifu Pharmaceutical University and on a DVD.The simulator is a teaching aid by which students can have dialogue with simulated patients created using computer graphics.There are 2 scenarios.In one of them the student conducts an initial interview and in the other he or she instructs a patient on medication compliance. Using these 2 methods,4 th-year students (n=68)of our university received instruction in medical communication and then a questionnaire survey was conducted.The results indicated that the training had been effective in enhancing students' knowledge of medical communication and helping them improve their communication skills (2-top ratio : 98.3%).As a result of the training,students' interest in this topic increased (2-top ratio : 74.1% for video,43.1% for simulator) and they found it useful as a means of self-learning (2-top ratio : 98.3% for video,22.9% for simulator) and as a way of learning communication skills (2-top ratio : 91.4% for video,25.0% for simulator).Covariance structure analysis showed that students were interested in additions to the curriculum that make use of videos and a simulator as they are useful in selflearning and learning communication skills.
As part of training in community pharmacy practices at our school of pharmacy,we conducted a training program aiming to enhance students’understanding of in-pharmacy drug products,and evaluated the change in their awareness of this subject afterwards,as well as their degree of satisfaction with the training and the degree to which they found it useful.The program consisted of giving students experience of the manufacturing process of particular in-pharmacy products and a case conference on them (Cold remedy No.13 A,topical 0.1% indomethacin solution and Keishi-to).We distributed a questionnaire to 111 students who took the training in 2009,and analyzed the responses of 101 who fully completed the questionnaire. After the training,about 90% of respondents selected“agree”or“strongly agree”as their responses to the statements“Inpharmacy drug products give customers a feeling of affinity with the pharmacy”,“In-pharmacy drug products are useful for gaining the trust of patients”,“In-pharmacy drug products show the characteristics of particular pharmacies”and“Dealing with in-pharmacy drug products is challenging”.Regarding the program content,the response rate for students who felt it was“useful”or“very useful”with regard to the case conference was close to 100%.Following this,the order of usefulness of content was packaging and labeling (99.0%),preparation of package insert (98.0%),manufacturing data record (97.0%),manufacturing (96.0-99.0%) and quality assessment (83.2%). The training on in-pharmacy drug product manufacturing processes included both pharmacological and pharmaceutical aspects and legal issues.Students found it to be beneficial in giving them a sense of the professionalism of the pharmacist as well as a feeling of the value of the pharmacist’s work and the responsibility that goes with it.Training on in-pharmacy drug products therefore has great potential in the education of pharmacy students.
Bone cement loaded with antimicrobial agents is used for the treatment and prevention of infections in orthopedic surgery.However,cases of acute renal failure associated with antibiotic-laden cement have recently been reported.In this study,the authors observed a marked change in vancomycin pharmacokinetics in 1 of 3 patients who had been implanted with vancomycin-loaded cement beads and were also receiving intravenously administered vancomycin.The pharmacokinetic parameters of vancomycin were estimated using VCM-TDM Ver.2 software for TDM based on the Bayesian estimation with a two-compartment model.Patient 1,a 67-year-old man with posterior lumbar interbody fusion,was operated on to implant vancomycin-loaded beads on day 25.The estimated clearance of vancomycin following implantation decreased from 60.3 to 6.17 mL/min,and the terminal half-life at the β-phase lengthened from 16.6 to 125 h,although the creatinine clearance decreased from 75.1 to 27.3 mL/min.Patient 2,a 73-year-old woman with posterior lumbar interbody fusion,was operated on to implant vancomycin-loaded beads on day 3.The estimated clearance of vancomycin was similar to the mean for the Japanese population.Patient 3 was a 69-year-old man undergoing total knee arthroplasty.The estimated clearance of vancomycin before implantation (34.4 mL/min) was half of the Japanese population mean (64.6 mL/min) but the estimated vancomycin pharmacokinetic parameters did not change after implantation.Patient 1 exhibited an unexpectedly high vancomycin serum concentration.Although the decrease in creatinine clearance in this patient could have markedly influenced the vancomycin pharmacokinetics,this would not fully explain what happened because the estimated vancomycin clearance after implantation (6.17 mL/min) was much smaller than the population mean clearance (21.8 mL/min).Our findings suggest that the change in pharmacokinetics was associated with the vancomycin-laden cement to some extent.Therefore,we need to closely monitor vancomycin parameters in patients who have been implanted with vancomycin-loaded beads and are also receiving systemic vancomycin therapy,in order to avoid nephrotoxity.
Gefitinib (Iressa®) plays an important role in the treatment of non-small cell lung cancer (NSCLC).However,antacids such as proton pump inhibitors (PPIs) and histamine H2 receptor antagonists have been seen to reduce the area under the blood concentration-time curve of gefitinib and are therefore designated as medicines that require caution when prescribed to patients receiving gefitinib. As it may be difficult to discontinue antacid therapy in patients receiving gefitinib,we examined how the clinical effects of gefitinib are modified by combination with antacids.Our subjects were 140 patients with NSCLC who were treated with gefitinib at our hospital between 2002 and 2009.We compared progression-free survival (PFS),overall survival (OS),objective tumor response and adverse effect rates in patients in receiving antacids as well (antacid combination group ; n=8citation=3)with those only receiving gefitinib (gefitinib only group ; n=57).We found that,except for patients receiving simultaneous administration of gefitinib with PPIs,patients in the antacid combination group exhibited no significant difference in PFS (3.7 months[2.0-5.4]vs.4.4 months[2.9-5.8],P=0.877),OS (17.2 months[12.1-22.3]vs.25.9 months[15.6-36.1],P =0.403),response rate (14.5% vs.19.3%,P=0.491),one-year survival rate (48.1% vs.48.1%,P=citation=1)or incidence of adverse effects,as compared to the gefitinib only group.Therefore,our findings suggest that,as long as simultaneous administration of gefitinib with PPIs is avoided,combination with antacids should not impair the clinical efficacy of gefitinib.