臨床薬理
Online ISSN : 1882-8272
Print ISSN : 0388-1601
ISSN-L : 0388-1601
15 巻, 4 号
選択された号の論文の12件中1~12を表示しています
  • 太田 道男, 眞島 澄子, 熊谷 頼佳
    1984 年 15 巻 4 号 p. 473-477
    発行日: 1984/12/30
    公開日: 2010/06/28
    ジャーナル フリー
    Optimization of warfarin administration was achieved theoretically using a mathe matical model for dose- patient dynamics. The criterion for optimization is to mini mize the time necessary to obtain the desired prothrombin levels . The patient model consists of linear and non-linear parts connected sequentially . The linear part is simply the 2- compartment model. The non-linear part is an exponential function of the linear part's output, which represents the time- independent relation between the serum dose density and the prothrombin time. The parameters in these models were identified for the mean values of the clinical data. By the discrete-time system theory, i. e. the finite time settling method, the optimal administration strategy was achieved for this patient model. The result agrees fairly closely with the empirical optimization.
  • Masaru MINAMI, Hiroko TOGASHI, Machiko SANO, Iwao SAITO, Hideya SAITO
    1984 年 15 巻 4 号 p. 479-487
    発行日: 1984/12/30
    公開日: 2010/06/28
    ジャーナル フリー
    One week of oral administration of Chinese Tienchi ginseng (500 mg/kg/day) produced significant decrease in blood pressure during the period of rapid rise in blood pressure in stroke-prone spontaneously hypertensive rats (SHRSP). At 20 weeks old, a significant difference in blood pressure was noted both between the pre-(218.3±9.7 mmHg) and post-(202.9±9. 2 mmHg) Tienchi treated groups (P<0.02) and between the non-drug control (217.3±6.8 mmHg) and the Tienchi treated SHRSP (P<0.02). These findings indicate that Tienchi ginseng produced significant inhibition of the hypertension development process in SHRSP.
  • 堀井 大治郎, 石橋 昭, 岩本 淳
    1984 年 15 巻 4 号 p. 489-495
    発行日: 1984/12/30
    公開日: 2010/06/28
    ジャーナル フリー
    The difference in bioavailability of nicorandil, a newly developed antianginal agent, before and after eating was studied in 10 healthy male volunteers. The phar macokinetic parameters after single oral administration of nicorandil (10 mg) were calculated by an automated pharmacokinetic analysis system according to a one-compartment open model. According to a statistical analysis, the values of Cmax, Tmax, [AUC] 0, Ke, and t1/2 in the bioavailability of nicorandil were not significantly affected by the ingestion of a meal, but that of Ka (apparent first order absorption constant) was significantly lowered by the ingestion.
  • 南 勝, 橋本 文教, 高村 一郎, 藤田 克裕, 安田 寿一, 斉藤 秀哉, 山口 定男, 山崎 泰志
    1984 年 15 巻 4 号 p. 497-506
    発行日: 1984/12/30
    公開日: 2010/06/28
    ジャーナル フリー
    To elucidate the relationship between captoprilinduced hemodynamic changes and pharmacokinetics, a dose of captopril 37.5 mg was administrated orally to patients with mild essential hypension (HYT: n=13) and normotensive healthy volunteers (NORM: n=11). An attempt was also made to clarify the relationship between humoral factors and hemodynamic changes. After captopril administration, systolic blood pressure (SBP) and diastolic BP (DBP) decreased significantly in HYT and NORM. However, heart rate (HR) did not change in either NORM or HYT. After captopril administration, humoral factors changed as follow: plasma renin activity (PRA) increased significantly in NORM, while insignificant increase of PRA was observed at the maximal SBP fall in HYT; plasma aldosterone concentration decreased significantly in HYT and NORM; plasma norepinephrine concentration (NE) increased significantly in NORM, while there was no statistically significant increase in plasma NE in HYT. No significant difference between the Tmax, Cmax and T1/2 of captopril was found in either HYT or NORM. AUC in HYT was significantly higher than that in NORM. Maximal BP fall was observed at T. after captopril administration in both groups. In HYT, the decreased SBP is associated with the pretreatment PRA. However, no significant correlation was discovered between ΔSBP and Delta;PRA. Captopril also produced a significant decrease in SBP and DBP in both lower-renin HYT and NORM.
  • 斎藤 洋三
    1984 年 15 巻 4 号 p. 507-516
    発行日: 1984/12/30
    公開日: 2010/06/28
    ジャーナル フリー
    The clinical effect of a new orally active anti-allergic agent, coded TA-5707 and chemically designed as 6-methyl-N-(1H-tetrazol-5-y1)-2-pyridine carboxamide sodium salt, was investigated in 12 male patients with allergic rhinitis. The drug was given orally in a single dose of 100mg. The skin and nasal porvocation tests were carried out with house dust.
    The results were as follows:
    1) Intracutaneous reaction at the threshold concentration was inhibited in 10 out of the 12 patients (83.3%). The inhibitory effect was stronger after 2 hr of administration than after 1hr of administration.
    2) In the nasal provocation test conducted in 2 patients, nasal symptoms and nasal mucosal findings were evidently improved in both patients 1 hr after administra tion. At 2 hr the nasal provocation reaction was completely inhibited in one patient and remarkably suppressed in the other patient.
    3) Neither subjective nor objective adverse reactions attributable to TA-5707 were observed in any patients.
  • 広田 徳子, 粕谷 泰次, 鬼海 靖彦, 宮田 昭三, 渋谷 正則, 松岡 和彦
    1984 年 15 巻 4 号 p. 517-524
    発行日: 1984/12/30
    公開日: 2010/06/28
    ジャーナル フリー
    For optimal theophylline therapy of asthma it is now strongly recommended to aim at plasma or serum levels of 10-20μg/ml. However, significant intrapatient variability in theophylline kinetics is often observed during the course of theophylline treatment. In the present study, 19 asthmatic children were repeatedly checked for theophylline clearance and were also clinically scored based on physical examina tions. Theophylline clearance values ranged from 0.034 to 0 .146 1/kg/hr among these patients. The highest percentage change in clearancewithin the same individual was found to be 48% . There was no significant relationship between changes in the clearance value and the clinical score (N=30, r=0.291). Dose-dependent eli mination kinetics of theophylline was indicated for some patients even within the desirable therapeutic serum concentration range. However, intrapatient variations in clear ance caused difficulties in assessing the dosedependent kinetics.
    Since large intrapatient variability can occur, a single determination of theophylline clearance cannot be used safely to predict future dosage requirements . It is necessary to monitor theophylline levels regulary even without changes in the dose, because significant variability in theophylline clearance with time may lead to disproportionate changes in plasma theophylline concentration with serious clinical consequences.
  • Sadao OHGUCHI, Mitsuyoshi NAKASHIMA, Hisakuni HASHIMOTO, Yoshiharu TAK ...
    1984 年 15 巻 4 号 p. 525-534
    発行日: 1984/12/30
    公開日: 2010/06/28
    ジャーナル フリー
    The effects of nadolol (Nad), indenolol (Idn), metoprolol (Met), pindolol (Pid), arotinolol (Art, S-596), and propranolol (Prp) on the cardiovascular system were studied noninvasively in healthy male volunteers. Exercise testing. with a bicycle ergometer was performed both before and after single oral administration of these β-blockers, and any changes in the exercise induced increase in heart rate systolic blood pressure product (ΔDP) were studied. Systolic time intervals were measured from the simultaneous recording of carotid pulse, phonocardiogram, and electrocardiogram at rest. Left ventricular dimensions were measured by echocardiography, and ejection fraction (EF), strokeindex (SI), and cardiac index (CI) were calculated by the standard techniques. Systemic vascular resistance (SVR) was computed from these data. ΔDP was decreased with all β-blockers. According to the degree of this effect, therelative potency of these drugs was estimated to be as follows: Pid > Art> Idn _??_Prp> Nad _??_ Met. The ratio of pre-ejection period to left ventricular ejection time was increased with all β-blockers. EF, SI, and CI were decreased by all β-blockers except Pid, by which SI and CI were kept almost unchanged, and EF was significantly increased. Therefore, Pid was thought to be less cardiosuppressive than the other β-blockers. SVR was significantly decreased by Pid, while it was increased by all the other β-blockers. These results suggest that the acute hemodynamic response to β-blockers is determined primarily by the property of intrinsic sympathomimetic activity. Neither β1-selectivity nor membrane stabilizing effect was shown to be a major factor modifying the central or peripheral hemodynamic response to β-blockers.
  • Bayesian 理論を用いた血中濃度データ解析
    堀 了平, 奥村 勝彦, 斉藤 一文字, 安原 真人, 越川 富雄, 橋田 亨, 奥野 武彦, 中川 照真, 山岡 清
    1984 年 15 巻 4 号 p. 535-544
    発行日: 1984/12/30
    公開日: 2010/06/28
    ジャーナル フリー
    A great deal of attention has been given to the problem of estimating the pharmacokinetic parameters of individual patients in order to optimize dosage choices. In the present study, the individual pharmacokinetic parameters of valproic acid were estimated using only 2 data points for each patients by a newly developed program, MULTI 2 (BAYES). This is a nonlinear multiple regression program based on the Bayesian method and written in BASIC for the microcomputer. From the information on the distribution of population pharmacokinetic parameters and plasma drug con centration measurements, MULTI 2 (BAYES) calculates the most likely set of para meters for the individual. The accuracy and precision of estimates were evaluated based on the difference between estimated and measured drug concentration. Selec tion of the population parameter set was found to affect the individual pharmacokine tic parameters estimated by MULTI 2 (BAYES). Using the population parameter set obtained from the data of patients in Kyoto University Hospital by NONMEM gave the most accurate estimates of individual patients by MULTI 2 (BAYES). Thus, use of a population parameter appropriate to the individual in question is necessary to obtain a good estimate of the individual parameter. This study provides significant evidence for the validity and usefulness of the Bayesian method in esti mating individual pharmacokinetic parameters from routine clinical data.
  • 西村 正治, 志田 晃, 鈴木 章彦, 田代 典夫, 稲葉 秀一, 川上 義和
    1984 年 15 巻 4 号 p. 545-554
    発行日: 1984/12/30
    公開日: 2010/06/28
    ジャーナル フリー
    The undesirable effects of two beta-blockers on pulmonary function were compared both in normal subjects and in stable asthmatic patients using a cross-over method.
    1. In 11 normal subjects, significant lowering of SGaw and FVC occurred at each observation point around 2 hrs after administration of timolol in contrast, no. signifi cant change was noted after arotinolol.
    2. In 6 patients with asthma in a stable stage, timolol reduced SGaw at 30 min, 1, 2, and 3 hrs after administration while arotinolol induced small reduction in only 30 min after the administration. The change by administration of timolol was significantly greater than that by arotinolol at any measured point.
    3. Two out of 6 patients experienced wheezing to a slight degree only after timolol.
    These results suggest that arotinolol, with its weak alpha-blocking action, will be safer for patients with asthma or chronic obstructive lung diseases than timolol, which shows potent effect on respiratory function even after occular topical use.
  • 東 威, 渡辺 暉邦
    1984 年 15 巻 4 号 p. 555-565
    発行日: 1984/12/30
    公開日: 2010/06/28
    ジャーナル フリー
    新抗炎症剤OXPの空腹時または食後投与および1日1回または分2投与における体内動態を把握するため, 健常成人男子を被験者とし, それぞれ単回投与試験および連続投与試験を実施し以下の結果を得た.
    1. 試験期間を通じて臨床検査値などに異常は認められなかった.
    2. 本剤400mg単回投与後の血清中濃度は4hrで最高濃度に達し, その後は約50hrの半減期で減少した.
    3. 本剤の体内動態は食事の有無によりほとんど影響を受けなかった.
    4. 単回投与後, 尿中へは主にOXPのエステルグルクロニドとして排泄され, ほかにM-3のエステルグルクロニド, M-2, M-3のエーテルグルクロニド, OXP, M-3の非抱合体などが認められた.
    5. 本剤400mgを1日用量とし1日1回または分2により連続投与した結果, いずれの場合も4~6日で定常状態に達し, その血清中濃度は単回投与時の約2倍であった.また平均血清中濃度は投与方法によらずほぼ一定値を示した.
  • 多施設二重盲検群間比較試験による検討
    新谷 博一, 吉田 文英, 水野 康, 福崎 恒, 安田 寿一, 蔵本 築, 戸嶋 裕徳, 村田 和彦, 佐久間 昭
    1984 年 15 巻 4 号 p. 567-583
    発行日: 1984/12/30
    公開日: 2010/06/28
    ジャーナル フリー
    The anti-anginal effect of nadolol was compared with that of propranolol . The present study was carried out as a multicenter, double-blind group-comparison, with the following results.
    1. The subjects were primarily patients with effort angina. Nadolol was administered in a single daily dose of 30 mg, while propranolol was administered in a daily dosage of 30 mg given in 3 divided doses, for 4 weeks each. When no effect was noted by the end of 2 weeks of treatment, the daily dosage of each was increased to 60 mg.
    2. There was no significant difference between the nadolol and propranolol groups in terms of clinical usefulness. The usefulness rate in the nadolol group was 80.0% (28/35), while it was 64.9% (24/37) in the propranolol group.
    3. In the evaluation performed by the physician-in-charge, the global improvement rates were 77.1% (27/35) for nadolol and 62.2% (23/37) for propranolol groups. There was no significant difference between these two rates. However, when only the cases of effort angina were considered, nadolol appeared to be superior to propra nolol.
    4. Heart rate was found to be significantly decreased in both the nadolol and prop-ranolol groups from the end of the first week of treatment in comparison with the rate prior to the drug treatment period. As for blood pressure, in the propranolol group significant decrease was seen only in the systolic blood pressure at the end of the 4th week of treatment, whereas in the nadolol group significant decrease was seen in both the systolic and diastolic blood pressures at the end of 2 weeks of treatment.
    5. Concerning the safety of the drug regimen, the percentages of patients not show ing any side effects of the drug were 86.0% (43/50) for the nadolol group and 92.3% (48/52) for the propranolol group.This difference was not statistically significant.
    In consideration of the fact that the nodolol regimen of a single daily dose gave these good results, it is concluded that nadolol is a more useful drug than proprano-lol for the clinical treatment of patients with angina pectoris.
  • 第一報: 点滴静注による単回および連続投与試験
    関本 博, 中野 利美, 松谷 芳英
    1984 年 15 巻 4 号 p. 585-603
    発行日: 1984/12/30
    公開日: 2010/06/28
    ジャーナル フリー
    Phase I study of S-adenosyl-L-methionine sulfate tosylate (FO-1561) was carried out with 17 healthy male volunteers by single administration and by multiple administrations 2-3 times daily for 2-3 consecutive days. In every case, FO-1561 was dissolved in the solvent, added to 500 ml of Ringer's solution, then administrated by intravenous drip infusion during about 2 hours.
    Subjective and objective symptoms and signs, physiological examination, hemato logical and biochemical examinations, analysis of blood gasses, urinalysis, and concentration of the drug in blood and urine were investigated during administration and up to 15 hours thereafter.
    The dose level was increased stepwise from single administration of 100 mg (the lowest dosage) to doses of 300 mg 3 times a day (900 mg/day) for 3 consecutive days (the highest dosage) while confirming safety.
    As a result, no abnormal symptom was observed except for a single case complaining of a slight and transient headache and feverishness, among the subjective and objective symptoms and signs. In physiological, hematological and blood biochemical examinations, no abnormal value was obtained, which was also the case with gasometricanalysis. In urinalysis, increase of urine volume and subsequent elevations of Na, K, Ca, and Cl in urine were observed in all cases, but these findings are due to the infusion of Ringer's solution and are regarded as a normal phenomenon in this case.
    Through the pharmacokinetic investigations, it was found that the plasma levels of the drug were elevated in proportion to the dose levels, reaching their maximum right after completion infusion and decreasing with a similar pattern of time course. About 60 % of the dosage was recovered unmodified in the urine within 6 hours after completion of the infusion. No accumulation was observed even in the case of multiple administrations.
    To conclude, it was confirmed that the drug could be administrated quite safely by intravenous infusion at doses less than 900 mg/day (300 mg × 3 times) for 3 consecutive days without any side effects, and that this treatment would be applicable to the clinical stage.
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