The presence of endogenous digoxin-like immunoreactive substance (DLIS) has been reported in several clinical conditions. Because DLIS is absent in protein-free ultrafiltrates of sera, the monitoring of the serum free glycoside concentrations (f-SGC) rather than the total glycoside concentrations (t-SGC) seems more appropriate. We conducted the present study to obtain basic information about monitoring f-SGC in patients receiving beta-methyldigoxin (BMD), using TDx digoxin assay.
The results showed that accuracy of the f-SGC detected with TDx assay is almost equal to t-SGC. Additionally, although the BMD-digoxin ratio has some influence on the evaluation of f-SGC, the impact seemed negligible if individual variance in the albumin concentration is taken into account. These findings suggest that the monitoring of f-SGC rather than t-SGC, is satisfactorily applicable in clinical situations.

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We prepared patient-oriented drug information sheets for 220 drugs, which were distributed to out-patients with acute or chronic diseases, or to parents of child patients. The effectiveness of providing the drug information sheets was evaluated by questionnaires which were received from 1396 patients with chronic diseases (chronic patients), 420 patients with acute diseases (acute patient) and 244 parents of child patients (parents). The results were as follows; 1) The drug information sheets were readable and understandable for most of the patients and the parents. 2) The percentage of those who feel difficulty in communicating with medical staffs was higher in acute patients and in parents than in chronic patients, however, the drug information sheets were equally effective in improving the relationship between doctors and acute patients, chronic patients and parents. 3) The percentage of those who feel anxious about prescribed drugs was high in young acute patients and in parents. The drug information sheets were effective in relieving their anxiety and in answering their questions about drugs. The present study showed that, although some revision of the information especially about the effects and adverse reactions of drugs might be necessary, the drug information sheets were beneficial almost equally for acute patients, chronic patients and parents.

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The efficacy of recombinant granulocyte-colony stimulating factor (G-CSF) has been shown in clinical trials. However, the high cost of G-CSF has led to concern about its beneficial effects in clinical practice.
Reviewing medical records of 57 gynecologic cancer patients with 250 courses of cytotoxic chemotherapy, we evaluated the effectiveness of G-CSF administration on the incidence of febrile neutropenia and on antibiotic usage. The courses were divided into two groups: “case” (post-marketing of G-CSF) and “control” (pre-marketing of G-CSF). Information on the blood cell count, regimen, age and number of days since the operation for both cases and controls was obtained from their medical records. Data of cases and controls were compared.
In the analysis of odds ratios from the logistic regression model, there were no significant differences between case and control groups in terms of the incidence of febrile neutropenia and antibiotic usage for the treatment of febrile neutropenia. On the other hand, the incidence of antibiotic usage for the prevention of infection was significantly high in the case group (p<0.05).
These results may indicate that the effectiveness in G-CSF usage is probably dependent on physician's decision-making in the administration of the above agents. Further studies are warranted on the effectiveness of pharmaceutical agents in clinical practice as well as clinical trials.

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The purpose of this study was to evaluate the effects of bunazosin, α₁-aradrenoreceptor blocking agent and metoprolol, a β₁-selective beta-blocker on the circadian variation and morning rise of blood pressure (BP) and heart rate (HR). In 26 untreated patients with mild to moderate essential hypertension, BP and HR were recorded using an ambulatory instrument (ABPM-630, Nippon Colin, Japan) for 48 hours every 30 minutes, before and after four weeks of treatment with bunazosin (n=12, 1 mg three times a day) or metoprolol (n=14, 40 mg three times a day). Mean 48-hour, daytime (awake), and nighttime (sleeping) systolic BP (SBP), diastolic BP (DBP) and HR values were analyzed by reviewing the patients' diaries. The nocturnal reduction rate of SBP, DBP and HR were calculated according to the following formula. Nocturnal reduction rate (%) = [(daytime mean-nighttime mean) /daytime mean] ×100. And then, “morning rise” of SBP, DBP and HR in the second day were calculated. Morning rise = [(mean values of 4 hours after awaking)-(mean values of 4 hours before awaking)]. In the pretreatment 48-hour mean, bunazosin lowered SBP by 6.8±4.4% (p<0.001) and DBP by 7.1±4.7% (p<0.001), but did not change HR. Metoprolol decreased the 48-hour mean of SBP by 6.1±4.9% (p<0.001), DBP by 9.1±5.7% (p<0.001) and HR by 12.3±7.4% (p<0.001). Nocturnal reduction rates of SBP and DBP showed no significant changes in either group.The morning rise of HR increased with bunazosin (p<0.05), but the morning rise of SBP, DBP and HR were significantly decreased with metoprolol (p<0.05).
These findings suggest that metoprolol causes reduction of morning rise of BP and HR without a significant change in circadian BP profile.

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The effect of age on the pharmacokinetics of a new thromboxane A₂ (TXA₂) receptor antagonist, S-1452, and the inhibitory effect on platelet aggregation were examined in young (24-31 years, n=8) and elderly (68-78 years, n=8) male subjects. Ten mg of S-1452 or placebo was given orally in a single-blind cross-over design.
Hepatic function estimated by indocyanine green (ICG) test decreased in the elderly [elimination rate constant of ICG; elderly: 0.161 (mean) vs. young: 0.192/min, p<0.05]. The maximum plasma concentration of S-1452 tended to be greater in the elderly than in the young [elderly: 28.7 (mean), young: 16.4 neml]. The ratio of the metabolites to unchanged compound in the C_max was significantly lower in the elderly than in the young [elderly: 1.1 (mean) vs. young: 1.7, p<0.05]. The inhibitory effect of S-1452 on platelet aggregation ex vivo induced by U-46619, a TXA₂ receptor agonist, persisted up to 6 and 9 hours after dosing in the young and elderly subjects, respectively.
These results suggest that the plasma concentration of S-1452 is higher, probably due to the reduced conversion of S-1452 to the metabolites, and the inhibition on platelet aggregation is prolonged in the elderly.

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Whether elderly patients can take prescription drugs as directed by a physician is often unclear. To assess capacity to comply with medication regimens in elderly patients, the authors have developed Japanese regimen adherence capacity tests (J-RACT). In the present study, 31 healthy volunteers (average age 41.6±12.1 years), 56 elderly inpatients (average age 72.7±6.9 years), and 70 elderly outpatients (average age 70.1±7.2 years) were examined by the J-RACT. Assessments with the J-RACT consisted of hearing, visual acuity, fingers dexterity, and a regimen comprehension scale (RCS) with simple questions regarding information on dosage and administration. Five different types of dispensed paper bags, which differed with respect to dosage and administration were used in the RCS. The subjects were questioned in an interview about taking the five drugs and their regimen comprehension was assessed with the RCS (maximum score: 10 points, lowest score: -10 points). Then regimen comprehension was classified into 4 grades: normal (10), caution needed (9 or 8), training needed (7 or 6), and assistance needed (5 or less). In addition, intelligence was tested with the revised version of Hasegawa's dementia scale (HDS-R). Nine of the 31 healthy volunteers (29.0%), 38 of the 53 elderly inpatients (71.7%), and 54 of the 68 elderly inpatients (79.4%) misunderstood some aspects of the regimens written on the paper bags. A poor comprehension of regimen was classified as “training needed” and/or “assistance needed” in 3 of the healthy volunteers (9.7%), 24 of the elderly inpatients (45.3%), and 33 of the elderly outpatients (48.5%), respectively. Seven elderly inpatients and 2 elderly outpatients classified as “assistance needed” and were suspected to have dementia because they had scores on the HDS-R of 20 or less. A significant correlation (Spearman's r=0.516) was noted between scores on the HDS-R and on the RCS in all of the subjects. The RCS revealed difficulties to comprehend regimen information on the paper bags in elderly patients. When prescribing for elderly patients with chronic diseases, it is important to evaluate their capacity to adhere to medication regimens with an index such as the J-RACT to determine the need for medication counseling before the start of a medication regimen.

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