GTH-42V is an intravenous infusion preparation of alendronate sodium hydrate, which is infused every 4 weeks for the treatment of osteoporosis. A clinical pharmacological study was conducted to examine the pharmacokinetics and safety of a single dose of GTH-42V infused intravenously over 30 minutes in 26 postmenopausal female subjects with normal renal function or renal insufficiency. In this study, the pharmacodynamics was also examined in an exploratory manner. As an index of renal function, estimated glomerular filtration rate (eGFR; mL/min/1.73 m²) was calculated for each subject from her age and serum creatinine level one day before the administration. The 26 subjects were divided according to eGFR into the following 4 groups: 7 with normal renal function (90 ≦ eGFR), 8 with mild renal insufficiency (60 ≦ eGFR < 90), 7 with moderate renal insufficiency (30 ≦ eGFR < 60), and 4 with severe renal insufficiency (15 ≦ eGFR < 30). C_max was similar regardless of renal function. AUC_0→∞ increased as renal function decreased, but mean AUC_0→∞ in subjects with severe renal insufficiency was around 1.4 times greater than in those with normal renal function. The time courses of percent change in bone resorption markers from baseline were similar in all the groups, indicating that GTH-42V would not cause excessive inhibition of bone resorption markers in subjects with renal insufficiency. Regarding the safety of GTH-42V, there were no adverse events (AEs) that were considered to be clinically important. Besides, the incidence of AEs did not differ significantly between the groups. These results indicate that GTH-42V can be used without dose adjustment in postmenopausal female patients with renal impairment. (Jpn J Clin Pharmacol Ther 2012; 43(6): 365-373)

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Objective: The aim of this randomized controlled trial (RCT) was to investigate the effects of pitavastatin on remnant-like lipoprotein particle cholesterol (RLP-C), which is known to be a risk factor for coronary artery disease.
Patients and Materials: Thirty patients with dyslipidemia were randomly assigned to the pitavastatin group (2 mg/day of pitavastatin plus salutary diet: n=15) or the control group (salutary diet only: n=15). Before and 4 weeks after randomization, the levels of RLP-C, together with apolipoproteins, pre-heparin lipoprotein lipase (LPL) mass and various lipids were measured under fasting conditions.
Results: The levels of RLP-C as well as apolipoproteins (apo B-100, apo E, apo C-II and apo C-III) and various lipids were significantly improved in the pitavastatin group but not in the control group. Meanwhile, apo B-48 and LPL mass were unchanged in both groups.
Conclusion: This RCT showed that administration of pitavastatin to patients with dyslipidemia significantly improved their RLP-C levels, compared with those of control patients with dyslipidemia. Thus, pitavastatin may be beneficial for decreasing RLP-C, which is a risk factor of atherosclerosis in patients with dyslipidemia. (Jpn J Clin Pharmacol Ther 2012; 43(6): 375-380)

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Background: The guidelines for prescription drug labeling were developed by the Ministry of Health and Welfare in 1997. More than ten years have passed, and various problems have arisen in the use of the prescription drug labels in clinical practice. The purpose of this study was to extract the problems regarding conditions for approval and to consider the measures for improvement.
Methods: A questionnaire survey on the attitudes of hospital pharmacists, community pharmacists, and doctors towards the conditions for approval for prescription drug labeling was conducted. The conditions for approval regarding newly approved drugs from March 2009 to March 2011 were also surveyed.
Results: In this survey, 43.3% of hospital pharmacists, 18.6% of community pharmacists, and 20.3% of doctors were aware that the conditions for approval are described in the prescription drug labels. Thirty-six of 131 newly approved drugs had 65 conditions for approvals, 60 (92.4%) of which concerned the appropriate use in clinical practice.
Conclusion: In order to attract medical professionals' attention, the conditions for approval should be described in the first part of the label. In addition, the contents of the conditions for approval should be described in a user friendly manner for health care professionals. Since there are some differences in the frequency of using the labels between pharmacists and doctors, if pharmacists would have a good understanding of the conditions for approval and communicate the contents to doctors, this may contribute to improve doctor's recognition of the conditions for approval. (Jpn J Clin Pharmacol Ther 2012; 43(6): 381-386)

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Background: Although calcium channel blockers are often used in hypertensive patients, information about the efficacy of generic calcium channel blockers is inadequate. The aim of the study was to verify that a generic product and a brand-name product of nifedipine have equivalent therapeutic effect in hypertensive patients on hemodialysis treatment.
Methods: Efficacy of nifedipine were evaluated in 77 hypertensive patients on hemodialysis in Sanai Memorial Hospital, who were switched from a brand product (Adalat^® CR) to a generic product (nifedipine CR “sawai”). We retrospectively reviewed their clinical records and evaluated the blood pressure data four weeks before and after switching.
Results: Systolic blood pressure and diastolic blood pressure were not significantly different between before and after switching (systolic/diastolic: from 148±14/77±11 mmHg to 150±16/78±11 mmHg; p=0.213/p=0.122). However, patients whose primary cause of renal failure was diabetes mellitus had uncontrolled high blood pressure after switching [OR 6.51 (95% confidence interval:1.86-22.79); p=0.003]. Patients who had been treated with dialysis for over 5 years also had uncontrolled high blood pressure after switching [OR 4.17 (95% confidence interval: 1.01-17.12); p=0.048].
Conclusion: Blood pressure control was not significantly different between the brand product (Adalat^® CR) and the generic product (Nifedipine CR “sawai”) in this study. However patients who have diabetes mellitus or have been on dialysis treatment for a long time should be monitored carefully after switching. (Jpn J Clin Pharmacol Ther 2012; 43(6): 387-392)

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There remains substantial controversy regarding the effect of concomitant use of clopidogrel and proton pump inhibitors (PPIs) on the clinical outcomes of patients who underwent coronary stent implantation. We examined the effect of concomitant use of clopidogrel and PPIs on the clinical outcomes after percutaneous coronary intervention (PCI) with coronary stent implantation. From our electronic medical record database, we identified 1,147 patients who had been prescribed clopidogrel (75 mg/day) between January 1, 2007 and March 31, 2011. A total of 420 patients were selected after excluding patients with cerebral infarction or carotid stenosis treated with clopidogrel, patients without coronary stent implantation, patients who were not followed by coronary angiography, and patients who discontinued clopidogrel. We stratified these patients into two groups: clopidogrel alone (n=186) and clopidogrel+PPI (n=234). For these patients, we retrospectively reviewed their electronic medical records to identify those with stent restenosis requiring treatment. Follow-up was until the first re-angiography. The primary outcome was a composite of stent thrombosis, rehospitalization for any reason, and all-cause death. The two groups did not differ significantly in the duration of follow-up; age; sex ratio; body mass index; smoking status; a history of hypertension, dyslipidemia, or diabetes; and the type of implanted stent. There were no significant differences between clopidogrel alone and clopidogrel+PPI in the rates of primary outcomes: stent thrombosis (0.54% vs 0.43%; p=1.0000), emergency hospitalization (1.61% vs 5.13%; p=0.0651), and death (4.3% vs 7.26%; p=0.2203). No significant difference was found between the two groups in the rate of stent restenosis (19.9% vs 18.9%; p=0.7090). Altogether, there was no significant difference in the total rate of these events (26.3% vs 31.2%; p=0.2819), and adjusted odds ratio for clopidogrel+PPI was 1.117 (95% confidence interval 0.703-1.780). In this study, concomitant use of a PPI was not associated with increased adverse clinical outcomes in patients treated with clopidogrel. Overall, because of the possible drug interaction between clopidogrel and PPIs through inhibition of the cytochrome P450 2C19 enzyme (CYP2C19), it would be difficult to predict adverse clinical outcomes after PCI with coronary stent implantation. In conclusion, the present results suggest that concomitant use of PPIs for gastric protection does not adversely affect the clinical outcome of patients who are receiving clopidogrel after PCI and are at increased risk of gastrointestinal complications. (Jpn J Clin Pharmacol Ther 2012; 43(6): 393-398)

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The electronic medical record system at Ehime University Hospital was changed in May 2009 due to a change from one computer company to another. Clinical research coordinators (CRCs) of the Clinical Therapeutic Research Center formed a Working Group to discuss various matters associated with clinical trials before this transition. One purpose of the Working Group was to establish a system to display the patients participating in clinical trial. Another was to consider a method that investigational drugs were prescribed. Soon after the system was changed, an unexpected, incomplete data migration was identified. Simple problems like this were solved immediately by reporting them to the Medical Informatics Division. Around the same time, clinical records written on paper were unified into the electronic medical record system. In the previous system, investigators had written assessment data on paper worksheets provided by sponsors. After the change, CRCs have developed templates and investigators input data into the template installed in the new electronic medical record system, so that the data is stored electronically. Actually, templates have been prepared for half of the clinical trials. Templates have not been made for the other trials because investigators are much more used to completing paper worksheets than inputting the data directly into the computer. This report will be beneficial for the clinical trial divisions of other hospitals and clinics that use the electronic medical record system. We should identify problems and work out solutions in order to promote electronic data recording. (Jpn J Clin Pharmacol Ther 2012; 43(6): 403-408)

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