[Evaluation of a Two-day Hospital On-site Training Program for Community Pharmacists: Approach to Facilitate Collaboration among Community Healthcare Professionals].

　The importance of community-based care systems has increased due to the highly aging population and diversity of disease. To enhance the cooperation among healthcare professionals in community-based care systems, a two-day on-site training program for community pharmacists based on a multidisciplinary team approach was conducted at the Medical Science Hospital of Shiga University from April 2015 to March 2017. There were two professional courses in this training program: the palliative care course and nutrition support course. Both courses consisted of common pharmaceutical care training as follows: regional cooperation among healthcare professionals, pharmacist's clinical activities in the ward, pressure ulcer care, infection control, and aseptic technique for parenteral solutions. Each course was limited to 2 participants. A questionnaire was given to participants in the training program. Seventy-five pharmacists participated in the training and all of them answered the questionnaire. According to the questionnaire, 86% of participants felt that 2 days was an appropriate term for the training program. Positive answers regarding the content of each program and overall satisfaction were given by 100% and 99% of the participants, respectively. In the categorical classification of free comments regarding the expected change in pharmacy practice after the training, both "support for patients under nutritional treatment" and "cooperation with other medical staff" were answered by 24 participants. These results suggested that the 2-day on-site training for community pharmacists facilitated cooperation among healthcare professionals in the community.

Effect of blood decrease on micafungin disposition in rats.

Micafungin (MCFG) is a novel echinocandin-class antifungal agent that extensively undergoes metabolic removal in the liver. In the present study, the influence of decreased blood volume on pharmacokinetic disposition of MCFG was examined using a rat model prepared by phlebotomy. In phlebotomized rats, hematocrit level and plasma albumin concentration were decreased by 50 and 15%, respectively. Regarding the pharmacokinetic parameters of MCFG, there were no significant differences in the total body clearance (CL(tot)) and elimination rate constant (k (e)) between control and phlebotomized rat groups. A slight increase was observed in the apparent volume of distribution at steady-state (Vd(ss)), but the degree of change was minimal. These findings demonstrate that the elimination capacity for MCFG is only slightly affected by severe anemia and moderate hypoalbuminemia, and provide experimental evidence for the preceding clinical studies suggesting that neither hematocrit level nor serum albumin concentration is a contributory factor for the metabolic clearance of MCFG.

Impact of plasma exchange on pharmacokinetic disposition of micafungin.

Change in the pharmacokinetic disposition of an antifungal agent micafungin (MCFG) by 8-hour plasma exchange (PE) with 3200 mL replacement was examined in a stem cell transplant recipient. On pharmacokinetic analysis of the time course of the serum concentrations of MCFG, it was determined that PE shortened the elimination half-life of MCFG from 16.5 hours to 6.3 hours. Total clearance (CL(tot)) was increased from 0.366 L/h to 0.932 L/h by PE. PE-dependent clearance (CL(pe)) accounted for approximately two-thirds of CL(tot), and PE was found to contribute to the removal of nearly 40% of the total body store of MCFG. It was confirmed that a significant amount of MCFG was excluded into apheresed plasma waste. In addition, adsorption of MCFG onto plasma-separating membrane was strongly suggested, because the CL(pe) exceeded the rate of plasma apheresis and MCFG concentrations in apheresed plasma were lower than those in circulating blood collected at the same time. The marked elimination of MCFG during PE can be explained by its low volume of distribution and high affinity for serum proteins. Judging from these findings as well as those of other reports, MCFG can be considered one of the drugs most susceptible to removal by PE. Our findings suggest that an increment in the regular dose of MCFG would be required at the next administration after PE.

Reduced elimination clearance of micafungin in rats with cholestatic hyperbilirubinemia.

We examined whether the pharmacokinetic disposition of micafungin (MCFG), an echinocandin class antifungal agent, is altered in hyperbilirubinemia using a rat model prepared by bile duct ligation (BDL). Serum bilirubin levels were increased depending upon the duration of BDL. The elimination rate constant and total body clearance (CL(tot)) of MCFG were reduced by 24% and 16%, respectively, after BDL for 1 h, but there was no significant change in the apparent volume of distribution at steady-state. The degree of reduction in the CL(tot) was much greater 7 days after BDL as compared with that 1 h after BDL (44% vs. 16%). However, the proportion of the biliary clearance in the CL(tot) was about 10%. This is similar to the extent of decrease in the CL(tot) by occlusion of the bile duct, demonstrating that decreased biliary excretion of MCFG makes only a minor contribution to its pharmacokinetic change. These findings suggest that the metabolic capacity of MCFG is markedly impaired in hepatic hypofunction secondary to hyperbilirubinemia, providing a fundamental explanation for the previous clinical report that there is a significant correlation between dose-adjusted plasma MCFG concentration and serum bilirubin levels.

Pharmacokinetic behavior of micafungin in rats with carbon tetrachloride-induced acute hepatic failure.

We examined the pharmacokinetic behavior of micafungin, a novel antifungal agent, in rats receiving carbon tetrachloride (CCl4) at a single dose of 2.5 ml/kg. There was no significant change in the total clearance (CL(tot)) in CCl4-treated rats, while the steady-state volume of distribution (Vd(ss)) was significantly increased by CCl4 treatment. Alteration in the serum unbound fraction of micafungin after CCl4 treatment was unlikely in light of the serum albumin, bilirubin, creatinine, and urea nitrogen. The increased Vd(ss) was attributable to augmentation in the accessibility of micafungin to peripheral tissue without impairment of the intrinsic clearance, because slight enhancement of the tissue distribution of micafungin was confirmed following CCl4 treatment.