Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics
Online ISSN : 1882-8272
Print ISSN : 0388-1601
ISSN-L : 0388-1601
Volume 14, Issue 3
Displaying 1-11 of 11 articles from this issue
  • Tokuji SUZUKT, Shoichi FUJITA, Jun KOZATANI, Toshimitsu OHKI
    1983 Volume 14 Issue 3 Pages 437-452
    Published: September 30, 1983
    Released on J-STAGE: June 28, 2010
    JOURNAL FREE ACCESS
    The usefulness of an approximation formula to calculate the power of analysis of variance for bioequivalence tests in a two-way crossover design was examined by comparison with the power estimated from the upper probability integrals of the noncentral F-distribution. The approximation formula was shown to be useful for the calculation of the power for usual bioequivalence tests . The calculation of the power for bioequivalence tests in a multi-way crossover design was attempted using the approximation formula.
    Further, data in previously published reports on bioequivalence between drug preparations were reviewed from the standpoint of the power. Only 24 of 86 bioequivalence analyses conducted with 25 different drugs gave a power higher than 80% to detect a 20% difference in bioavailability with α=0.05, and the power of about a half of the analyses was lower than 50%.
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  • Relationship between Change in Osmotic Resistance of Erytrocyte Membrane and Forecast Adverse Reaction
    Saizo YANAURA, Hidetoshi MITO, Aiko KOBAYASHI, Tomoo NISHIMURA, Fujio ...
    1983 Volume 14 Issue 3 Pages 453-461
    Published: September 30, 1983
    Released on J-STAGE: June 28, 2010
    JOURNAL FREE ACCESS
    Theophylline (TP) plasma concentration and change in the osmotic resistance of erythrocyte membrane, following oral administration of aminophylline, were studied in ambulatory bronchial asthmatic children.
    The osmotic resistance of erythrocyte membrane was measured by coil planet centrifuge system.
    In normal adults and asthmatic children, hemolysis starting point was shifted to the lower side of osmotic pressure, and the osmotic resistance of erythrocyte membrane were increased after administration of TP.
    In patients with past adverse reactions of TP derivation, the time to the peak of the osmotic resistance were at the same time or shorter than that to the peak plasma concentration.
    It suggested that relationship between the peak TP plasma concentration and change in osmotic resistance might be enable to forecast adverse reaction.
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  • Hiroyuki MATSUMOTO, Etsuro ITO
    1983 Volume 14 Issue 3 Pages 463-469
    Published: September 30, 1983
    Released on J-STAGE: June 28, 2010
    JOURNAL FREE ACCESS
    Acebutolol, a relatively weak lipophilic nature in comparison to propranolol, possesses cardioselectivity and membrane-stabilizing properties without intrinsic sympathomimetic action. This betai-selective blocker may affect central nervous activity, judging from the effectiveness for essential tremor and the central nervous system side-effects although the incidence has been low as compared to propranolol. In order to prove this hypothesis, the present study aimed to demonstrate acebutolol penetration into the central nervous system by the use of autoradiography.
    Male Sprague-Dawley rats weighing approximately 300 g received 7.5 mg (188.25 μ Ci) of 14C-acebutolol hydrochloride in 0.5 ml of physiologic saline within 30 seconds from the femoral vein. After 5 minutes the animals were decapitated, and the brains were quickly removed and frozen. Subsequently, the sections 20 μ thick were prepared, which were subjected to autoradiography.
    The areas accumulating the highest radioactivity were the ventricles, the cisterns and the tuber cinereum, where the blood brain barrier is lacking. Besides these areas a moderate radioactivity was observed at the mammillary bodies. However, no other parts of the central nervous system revealed a significant location of radioactivity.
    From the above results, it was concluded that 14C-acebutolol and possibly its metabolites easily penetrate into cerebrospinal fluid, and the presence of selectively accumulating sites in the central nervous system, if any, has to be pursued in a time-course disposition study.
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  • Masashi SASA, Hiroshi NAITO, Alan Bye, Paul Whiteman
    1983 Volume 14 Issue 3 Pages 471-479
    Published: September 30, 1983
    Released on J-STAGE: June 28, 2010
    JOURNAL FREE ACCESS
    The pharmacokinetics of acyclovir (ACV) was studied in 8 healthy male volunteers. Half of the men were given 5 mg/kg (group 1) and half were given 10 mg/kg (group 2). ACV was dissolved in 180 ml of saline and intravenously perfused for one hour. At the end of the perfusion group 1 and group 2 respectively demonstrated: mean half life value of slow phase (t1/2 β) of 2.50 and 2.45 hr, and mean area under the plasma concentration-time curve (AUC0) of 71.6 and 131.3 μmol h/1. Combined data from both groups revealed: mean volume of distribution at the steady state (Vdss) of 47.0 1, a mean whole body clearance of 336.6 ml/min. The mean renal clearance was 242.4 and 221.7 ml/min as determined by the area method and elimination rate method, respectively. These clearances exceeded the normal glomerular filtration rate, indiccating renal secretion of ACV in addition to glomerular filtration. The mean urinary elimination of unchanged ACV was 62.8 and 72.3% of the administered dose within 6 and 48 ht after infusion started, respectively. No clinical or laboratory evidence of toxicity was noted in the 8 subjects examined.
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  • Tsutomu KIDOKORO, Yozo WATANABE, Mitsugu SUGIYAMA, Yukichi MORIYAMA, H ...
    1983 Volume 14 Issue 3 Pages 481-494
    Published: September 30, 1983
    Released on J-STAGE: June 28, 2010
    JOURNAL FREE ACCESS
    A double-blind controlled study was conducted in order to compare the analgesic effects of cyclazocine (0.3 and 0.5 mg) and pentazocine (15 and 30 mg) administered intramuscularly. The subjects were 363 post-operative patients having severe pain following abdominal surgery with halothane/N2O, enflurane/N2O or neuroleptanesthesia.
    Pain intensity and sedation scores were recorded at 0.5, 1, 3 and 6 hours after injection. of 363 patients, 346 were subjected to general analysis and 17 to safety analysis only.
    Cyclazocine 0.5 mg and pentazocine 30 mg were superior to pentazocine 15 mg in analgesic effect; statistically significant differences (p<0.05) in analgesic efficacy were found between cyclazocine 0.5 mg and pentazocine 15 mg; and between pentazocine 30 mg and pentazocine 15 mg.
    In the overall utility rating, the rates of usefulness of cyclazocine 0.3 and 0.5 mg and pentazocine 15 and 30 mg were 67.8, 80.7, 60.0 and 80.2% respectively. The contrasts in clinical usefulness of cyclazocine 0.5 mg as well as pentazocine 30 mg against pentazocine 15 mg were statistically significant (p<0.05).
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  • Yuichi KOIKE, Masayuki SAKURAI, Noriyoshi KATO, Miri FUJITA, Tetsuo NI ...
    1983 Volume 14 Issue 3 Pages 495-506
    Published: September 30, 1983
    Released on J-STAGE: June 28, 2010
    JOURNAL FREE ACCESS
    Ten mg of verapamil was administered intravenously to eight patients with paroxysmal supraventricular tachycardia. After drug administration, investigation of the pharmacokinetics of verapamil was carried out, and the relationship between plasma verapamil concentration and its electrophysiological effects was studied. After verapamil administration, pharmacokinetic parameters were calculated using a two-compartment open model. Biological half-life ranged from 2.91 to 4.55 hours and apparent volume of distribution ranged from 1.28 to 3.18 L/kg. Total body clearance ranged from 216 to 733 ml/min.
    Verapamil significantly prolonged the AH interval but did not prolong the HV interval. The effective and the functional refractory period of the AV node (ERPAVN and FRPAVN) were also prolonged after verapamil administration. The antegrade echo zone and the supraventricular tachycardia zone were also narrowed in most patients. A concentration-dependent relationship between plasma verapamil andpercent increase of both ERPAVN and AH interval was observed.
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  • Yoshio UDAKA, Yoichiro FURUKAWA, Takeshi MIZUNO, Toshihiro SAITO, Yosh ...
    1983 Volume 14 Issue 3 Pages 507-513
    Published: September 30, 1983
    Released on J-STAGE: June 28, 2010
    JOURNAL FREE ACCESS
    The hemodynamic effects of mexiletine, lidocaine, procainamide and disopyramide were compared using 12 healthy volunteers.
    We used physiological saline as control. Twenty ml of saline (control), 100 mg of mexiletine, 100 mg of lidocaine, 500 mg of procainamide and 100 mg of disopyramide, respectively, were injected intravenously in the time span of 5 min. to the same subjects at an interval of one week. Lidocaine was found to be prone to increase heart rate, but showed hardly any effects upon cardiac index or total peripheral vascular resistance. Procainamide increased heart rate and showed reduction in systolic blood pressure and a trend of decrease in total peripheral vascular resistance slightly. Disopyramide exhibited hardly any effects upon the systolic blood pressure, but elevated the diastolic blood pressure remarkably. Despite the increased heart rate, a tendency of reduction in the cardiac index was noted and the stroke volume index decreased appreciably.
    The pre-ejection period (PEP) was increased and the ratio of ejection time (ET) versus pre-ejection period was decreased. Hardly any changes were noted in the QTc on EKG with mexiletine and lidocaine, whereas the QTc in procainamide and disopyra mide tended to be lengthened.
    It is clearly shown by the above findings that the intravenous injection of 100 mg of mexiletine for 5 min. caused no adverse effects upon the hemodynamics. On the other hand, it was found advisable to take precaution in the use of disopyramide for patients with cardiac dysfunction, since its intravenous injection in a dose of 100 mg for 5min. showed the decrease in cardiac index and in stroke volume index and the increase in total peripheral vascular resistance.
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  • Yoshihisa WAKABAYASHI
    1983 Volume 14 Issue 3 Pages 515-528
    Published: September 30, 1983
    Released on J-STAGE: June 28, 2010
    JOURNAL FREE ACCESS
    1) Three lots of GV-523 (polyethylene glycol treated human immunoglobulin, lyophilized) were tested in administering intravenously to 5 normal volunteers at the dose of 2, 500 mg and to 3 volunteers at the dose of 100 mg/kg body weight. There was no significant adverse reaction during 3 weeks of the observation period.
    2) An increase of C-reactive protein was observed in the serum of one volunteer after 11 days of the administration (at the dose of 2, 500 mg), but a direct relationship with GV-523 administration was not evident.
    3) Three repeating administration of each 2, 500 mg of GV-523 to 3 volunteers at the intervals of 3 weeks gave no significant adverse reaction and no antigenicity was proved at the passive cutaneous anaphylaxis test in guinea-pig with the use of the volunteer's sera up to 9 weeks.
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  • Ryuichi KATO, Yasuaki UJI, Minoru YUI, Shoji TANJI
    1983 Volume 14 Issue 3 Pages 529-544
    Published: September 30, 1983
    Released on J-STAGE: June 28, 2010
    JOURNAL FREE ACCESS
    The sustained-release capsule of urapidil (BKU), a new antihypertensive currently on the West German market as Ebrantil®, was studied in a phase 1 trial with doses ranging 15-90mg (1/ (2-3) times the German dosage), and the results obtained were as follows:
    1. Orthostatic disorders, side effects on the central nervous system and vasodilative symptoms and gastrointestinal disorders were found dose-dependently. These mild symptoms were occurred mostly 4 hr after administration in related with the plasma levels and thereafter disappeared.
    2. Blood pressure was lowered at the dose of 60mg in the standing position and 90mg in supine, sitting and standing position. No other drug-related changes were observed in heart rate, electrocardiogram and laboratory findings.
    3. In pharmacokinetic studies, the present results were in agreement with thoseobtained with German volunteers, and detectable racial differences were not observed. In a total of 18 cases, T1/2 and maximum plasma concentration time (Tmax) were 3.2±0.3hr (mean± S.E.) and 3.8±0.2hr, respectively. Maximum plasma concentration (Cmax) and AUC were dose-dependent. Recoveries in 24 hrurine were11.8±1.8% to 18.3±3.1% for the unchanged, 20.8±4.3% to 30.8±1.8% for hydroxylated metabolite and 2.2±0.4% to 2.9±0.6% for N-demethylated metabolite.
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  • Multi-Center Well Controlled Comparative Study
    Kanji SHICHIKAWA, Mitsuo IGARASHI, Sachiko SUGAWARA, Yoshio IWASAKI
    1983 Volume 14 Issue 3 Pages 545-558
    Published: September 30, 1983
    Released on J-STAGE: June 28, 2010
    JOURNAL FREE ACCESS
    The usefulness of high molecular weight sodium hyaluronate (SPH) on osteoarthritis of the knee was examinedby a well controlled comparative study using 5.0ml of 0.5% SPH solution (S) or 5.0ml of 0.01% SPH solution (P) for intra-articular injection. Sixteen institutions participated in this study.
    1. Total number of patients examined was 107, in which the number of S group was 52 and that of P group was 55. Among those patients, 98 (S group 48; P group 50) were adopted for the analysis of final global improvement and usefulness, and 103 (S group 50; P group 53) for the analysis of general safety.
    2. Five intra-articular injections in total were given in weekly intervals. The final global improvement, general safety and usefulness were evaluated. The S group was significantly superior to the P group in terms of the final global improvement and usefulness. No significant difference was observed between S and P groups in terms of general safety.
    3. Effectiveness on SPH for the pains on movement was proved, as shown in the improvement of the objective and subjective symptoms as well as the activities of daily living related to the pains.
    4. As adverse side effect, local pain after injection of drugs was observed in one case of S group (1/50) and in one case of P group (1/53), and rash was observed in one case of P group (1/53). However, these symptoms were mild or moderate and disappeared by discontinuing the injection of the drugs. Laboratory examination showed no abnormal findings being caused by the drugs.
    5. As SPH is effective for the pains on movement and caused almost no side effect, it is considered that SPH is a useful drug for the treament of osteoarthritis in which pain is the main complaint of the patients.
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  • 1983 Volume 14 Issue 3 Pages e1
    Published: 1983
    Released on J-STAGE: February 25, 2011
    JOURNAL FREE ACCESS
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