The aim of the present study is to investigate difference in sensitivity to glibenclamide, a sulfonylurea oral antidiabetic agent, among Wistar rats, Spontaneously Hypertensive rats (SHR/Izm) and Wistar-Kyoto rats (WKY/Izm). We examined the effect of glibenclamide on blood levels of glucose and insulin in these rat strains. Under anesthesia with pentobarbital sodium (50 mg/kg, i.p.), blood samples were collected before and 5-120 min after administration of glibenclamide (10 mg/kg, i.p.). Blood levels of glucose and insulin in each sample were measured by glucose oxidase method and radioimmunoassay, respectively. In 8 week-old rats of all strains tested, blood levels of glucose were decreased by glibenclamide. In 12-20-week-old rats, although blood levels of glucose in Wistar and SHR/Izm were decreased after glibenclamide administration, those of WKY/Izm were not decreased. In rats of this age, time-course and extent of increases in blood insulin levels observed after administration of glibenclamide in WKY/Izm was almost the same as that of SHR/Izm, however, smaller than that of Wistar. Both insulin secretions induced via inactivation of ATP-sensitive K ؉ channel and sensitivity of pancreatic b b-cells to insulin seems to be decreased in WKY/Izm after 12 weeks of age. This phenomenon may explain the mechanism of glucose intolerance previously reported in WKY/Izm.

4In collaboration with orthopedic surgeons, we have developed and introduced a protocol for pharmacists with the aim of providing support for the prescription of analgesics used for pain associated with orthopedic areas. The prescription support mainly involves changes in the dose and administration of continually administered analgesics. This includes increasing, reducing, or discontinuing doses, as determined by the ward pharmacist in charge on the basis of the severity of the patient＇s pain. In the six-month period following the introduction of this protocol, 164 prescription entries (140 for oral drugs, 24 for external drugs) were made by pharmacists. For both oral and external drugs, the drugs prescribed were those having a high frequency of prescription at the hospital. Of the prescription entries for oral drugs, 94 were made for continued prescriptions. In addition, 18 were made for changes to prescriptions as needed and deletion, and 10 were for dose reduction. No adverse events were observed. All physicians who participated in the trial rated the protocol highly, and to justify their rating, many described the protocol as a procedure that ＂reduced the operational load for physicians.＂ Many physicians requested expansion of the scope of this protocol, and all physicians stated, ＂I wish this protocol was introduced for other drugs.＂ Although the protocol was found to be highly beneficial, it is important to discuss physicians＇ responsibilities in cases of adverse events.