[Performance of a portable continuous infusion pump (SUREFUSER A) in continuous infusion of 5-FU].

Therapy with mFOLFOX6/FOLFIRI used in treating colorectal cancer is typical of the regimens performed in outpatient settings. In this therapy, 46-h continuous infusion of 5-fluorouracil (5-FU) with concomitant oxaliplatin and irinotecan hydrochloride is conducted. The portable continuous infusion pump that makes continuous infusion possible has a non-electric structure, so variation in the infusion rate is seen. There are known effects of 5-FU concentration and temperature, and many studies have reported on the precision. In our hospital, we have experienced many cases of incomplete infusion and delays for the above reasons. We changed the specifications of the infusion pump to correspond to the kinematic viscosity of 5-FU and made all drug solution amounts uniform. We measured the time required to administer the drug solution from the time the infusion was started (recorded by a nurse) and the time it was completed (recorded by the patient), and confirmed the precision of the pump after the changes were made. It was found that while there was a decrease in the infusion rate at which the effect of the kinematic viscosity of 5-FU is seen, the mean infusion time was kept to within 46+/-10% hours in more than 90% of patients. There were no effects from concentration differences in 5-FU, and the completion time was reduced. The management and lifestyles of individual patients are potential factors in precision errors, and it is important to explain in advance to patients the necessity of secure fixation and infusion pump problems that might occur.

[Histories of the Japanese Red Cross Society and Department of Pharmacy, Nagoya Daini Red Cross Hospital].

The International Red Cross Society was founded in 1863 under the advocacy of Henri Dunant. More than ten years later, in 1877, the predecessor to the Japanese Red Cross Society, called the Philanthropic Society, was established during the Satsuma Rebellion by Tsunetami Sano, Yuzuru Ogyu, and others. Sano was the head of the Genroin (a council of elder statesmen) and later a Count. This year marks the 129th anniversary of the founding of the Japanese Red Cross, but its founding philosophy of giving aid to soldiers injured on the battlefield, regardless of whether they are friend or foe, has lived on to the present. Although the Japanese Red Cross received international criticism for not working more actively on behalf of the several hundred thousand prisoners held by Japan during World War II, its overall history for the past 129 years has been one of respecting humanity. The Nagoya Daini Red Cross Hospital celebrated the 92nd anniversary of its opening in 2006. Compared with its beginnings, the hospital has come a great distance in terms of both facilities and personnel. The number of outpatients per day has grown from none to 1,854, while the number of prescriptions per year has increased from 0 to 22,000. There has also been a sharp increase in the number of pharmacists, from 0 to 34. Over these many years, our hospital operations have continued to evolve to meet the needs of the time.

EGFR mRNA is upregulated, but somatic mutations of the gene are hardly found in renal cell carcinoma in Japanese patients.

PURPOSE: Heterozygous somatic mutations of epidermal growth factor receptor (EGFR) in exons 18, 19, and 21 were recently reported to be associated with response to gefitinib in patients having nonsmall cell lung cancer. Such mutations are more frequently found among Japanese than Europeans. In this work, the frequency of mutations was investigated in renal cell carcinoma (RCC) samples obtained from Japanese subjects to examine the potential of gefitinib as a therapeutic agent for RCC. METHODS: Nineteen patients with RCC, who gave written informed consent, were enrolled in this study. mRNA expression levels of EGFR were measured in RCC and its adjacent noncancerous renal tissue via the real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. Somatic mutations were determined using genomic DNA extracted from RCC by direct sequencing method. RESULTS: mRNA expression was confirmed to be about 19 times higher in RCC than in adjacent noncancerous renal tissues, but no such mutations were detected in both. CONCLUSION: Results from this study do not support the validity of further clinical trials on gefitinib for RCC with genotyping even in Japanese patients, although EGFR plays a key role in tumor progression.

Dose adjustment strategy for oral microemulsion formulation of cyclosporine: population pharmacokinetics-based analysis in kidney transplant patients.

The present study aims to determine the population pharmacokinetic parameters of cyclosporine (CsA) after multiple oral administration of the microemulsion formulation, Neoral, in kidney transplant patients and to propose a limited sampling strategy to predict AUC(0-4h) using them and the Bayesian method. The AUC(0-4h) is a parameter that has recently been recommended as an index for the dose adjustment in therapeutic drug monitoring of CsA. Blood samples were obtained at the trough level and at hourly intervals up to 5 hours from 125 patients (78 male and 47 female) who were receiving Neoral twice daily, and whole-blood concentrations of CsA were measured. The population pharmacokinetic parameters were estimated using the NONMEM computer program and a linear two-compartment model with first-order absorption. The observed AUC0-4h and concentrations at different sampling times were compared with those computer-predicted by the Bayesian method, using the population pharmacokinetic parameters and 2 or 3 concentrations from those at 0 h (C(0)), 1 h (C(1)), and 2 h (C(2)) after administration. Typical values for the absorption rate constant (k(a)), elimination rate constant (k(el)), apparent volume of distribution for the central compartment (Vd/F), and oral clearance (CL/F) calculated by population pharmacokinetic analysis were 2.16 hours(-1), 0.547 hours(-1), 43.3 L, and 23.7 L/h, respectively. The CsA concentrations predicted using either the 2-point or 3-point sampling strategy exhibited an excellent correlation with the observed values (R(2) > 0.81), and accordingly, the predicted AUC(0-4h) values were in excellent agreement with those observed. The best predictability of AUC(0-4h) was found for the 3-point sampling strategy using C(0), C(1), and C(2), closely followed by a 2-point sampling strategy using C(1) and C(2). The present findings suggest that a simplified strategy based on population pharmacokinetics can accurately predict AUC(0-4h) from concentrations at 2 or 3 sampling time points, providing an excellent method for the daily dose adjustment of Neoral in routine clinical use for kidney transplant patients.

Comparative absorption of 5-aminosalicylic acid (5-ASA) after administration of a 5-ASA enema and salazosulfapyridine (SASP) after an SASP suppository in Japanese volunteers.

Salazosulfapyridine (SASP) is widely used orally and rectally in the treatment of ulcerative colitis. SASP is mainly metabolized by hydrolysis and the main active metabolite, 5-aminosalicylic acid (5-ASA), has an antiinflammatory effect. In the present study, we prepared suppositories containing 6.5 mmol of SASP and an enema containing 6.5 mmol of 5-ASA. We measured the concentrations of SASP and its various metabolites, 5-ASA, sulfapyridine (SP), acetylated metabolite of SP (Ac-SP), and N-acetyl-5-ASA (Ac-5-ASA), in the serum and urine after a single administration of each preparation to healthy male volunteers. When the SASP suppository was administered, the maximum concentration (Cmax) of SASP and Ac-5-ASA was 2.5+/-0.4 and 0.5+/-0.2 microM and the time to Cmax (Tmax) was 5 and 12 h, respectively. The Cmax value of SP, which causes side effects, was one-half of that of the parent compound. No 5-ASA in the serum was observed. When the 5-ASA enema was administered, Cmax and Tmax values of 5-ASA and Ac-5-ASA were 5.8+/-2.0 and 13.3+/-3.6 microM and 1 and 7 h, respectively. The area under the serum concentration-time curve (AUC) of SASP was 27.4+/-4.8 microM x h, a finding similar to that of 5-ASA after the administration of the 5-ASA enema (29.4+/-11.1 microM x h). The percentage of urinary recovery of SASP 24 h after administration of the SASP suppository was approximately 0.2%. These results indicate that SASP administered rectally is almost completely hydrolyzed in the colon and that 5-ASA is partially absorbed from the small intestine in unchanged form. On the other hand, approximately 0.3% of 5-ASA was recovered in the urine in unchanged form after the administration of the 5-ASA enema, whereas the urinary recovery of Ac-5-ASA was more than 10%. The present findings suggest that 5-ASA has favorable absorptive properties and can be expected to have systemic action after rectal administration of a 5-ASA enema.