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Volume 24 (1993)
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Virtual issue
Volume 24, Issue 4
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1993 Volume 24 Issue 4 Pages 59E
Published: 1993
Released on J-STAGE: February 25, 2011
JOURNAL FREE ACCESSDownload PDF (813K) -
Isao KOHNO, Ikuo TSURUTA, Hiroyuki ISHII, Takao KOMAYA, Shigeo MUKAIYA ...1993 Volume 24 Issue 4 Pages 541-549
Published: December 31, 1993
Released on J-STAGE: June 28, 2010
DOIhttps://member-cnki-net-s-1416.res.gxlib.org.cn:443/rwt/1416/https/MSYXTLUQPJUB/10.3999/jscpt.24.541JOURNAL FREE ACCESSAn open and non-randomized study was performed employing 10 patients (average age 54 years, 6 male and 4 female) with untreated essential hypertension to evaluate the efficacy on the circadian variation of blood pressure of bunazosin hydrochloride for more than 4 weeks. Mean values of systolic and diastolic blood pressure and heart rate for 48 hours every 30 minutes were obtained before and after the treatment using a noninvasive ambulatory monitor (model ABPM-630, Nippon Colin Inc., Japan). Each patient was administered bunazosin hydrochloride at a dose of 1 mg t. i. d. for more than 4 weeks. The data were analyzed with a conventional statistical method, hyperbaric index and the cosinor method during the day active and the night resting span, respectively. Systolic blood pressure (SBP) was significantly decreased from 160±6 to 152±7 mmHg (P<0.05) during the day active span, but this decrease was not significant during the night resting span. Diastolic blood pressure (DBP) also decreased significantly during the day active span, but not significantly during the night resting span. Hyperbaric indices and fractionated hyperbaric indices (hyperbaric index for every 4-hours) did not show a change in systolic and diastolic blood pressure or heart rate. MESOR (midline estimating statistic of rhythm) decreased significantly in SBP (p<0.05) and in DBP (p<0.01), however, circadian amplitude and acrophase did not change. 48-hour mean, means during the day active and during the night resting span, MESOR, amplitude and acrophase in heart rate did not show significant changes. In summary, bunazosin hydrochloride had antihypertensive effects on SBP and DBP especially during the day active span, but these were less effective on SBP and DBP during the night resting span and heart rate by this regimen.View full abstractDownload PDF (1121K) -
Tatsuyuki MATSUNAMI, Mitsuhiro YOKOTA, Masahiko UKAI, Yasuto NISHINAKA ...1993 Volume 24 Issue 4 Pages 551-562
Published: December 31, 1993
Released on J-STAGE: June 28, 2010
DOIhttps://member-cnki-net-s-1416.res.gxlib.org.cn:443/rwt/1416/https/MSYXTLUQPJUB/10.3999/jscpt.24.551JOURNAL FREE ACCESSEffects of carperitide on cardiac function during dynamic exercise were studied in 11 patients, aged 50 to 68 years, with chronic heart failure.
Changes in hemodynamic parameters during symptom-limited supine multistage bicycle ergometer exercise testing, in which initial work load of 25 w was increased stepwise by 25 w every 3 min, were compared before and after intra-pulmonary artery infusion of carperitide (0.05 or 0.1μg/kg/min, for 30 min).
Following carperitide infusion at rest, systolic and diastolic blood pressure, systemic vascular resistance and pulmonary artery wedge pressure decreased significantly, while the heart rate increased signficantly.
At the time of peak exercise, the pulmonary artery wedge pressure remained at a lower level (13.5±2.9mmHg ; mean±SEM) after the infusion of carperitide as compared to the case of placebo infusion (25.1±2.4mmHg, p<0.001). Other hemodynamic parameters including blood pressure, heart rate, cardiac index, coronary sinus flow, systemic vascular resistance, coronary vascular resistance, and myocardial oxygen consumption showed no significant diffe- rences between the carperitide and placebo groups.
One of 2 patients receiving 0.1μg/kg/min of carperitide was withdrawn from the study due to the occurrence of abrupt hypotension. None of 9 patients receiving 0.05μg/kg/min experienced any adverse effect.
These results suggest that infusion of carperitide at a moderate dose can exert some beneficial hemodynamic effects on exercise-induced impairment of left ventricular function in patients with chronic heart failure.View full abstractDownload PDF (1482K) -
Comparison between AUC Monitoring and Trough Level MonitoringYoshimitsu YUHKI, Yoshikazu GOTOH, Kohji TADANO, Yasushi TAKAHASHI, Ke ...1993 Volume 24 Issue 4 Pages 563-570
Published: December 31, 1993
Released on J-STAGE: June 28, 2010
DOIhttps://member-cnki-net-s-1416.res.gxlib.org.cn:443/rwt/1416/https/MSYXTLUQPJUB/10.3999/jscpt.24.563JOURNAL FREE ACCESSRecent studies have suggested that the measurement of the areaunderthe-curve (AUC) is a more effective method of controlling cyclosporine (CYA) therapy . This paper has investi gated the use of AUC monitoring compared with trough level monitoring.
CYA (dose: 1.6-8.3mg/kg/day) was administereted orally to 28 renal transplant patients (10-52 years old). Blood specimens were collected at trough level, 1, 2, 3, 6, 8 and 12 hr or trough level, 1, 3 and 6 hr to determine the whole blood concentration of CYA . The AUC was calculated by the trapezoidal method or multiple linearregression method.
The correlation coefficient of AUC and the trough level with the administereted oral dose, expressed as mg/kg/day by the polynomial method, were 0.435 and 0. 380, respectively. The correlation coefficient between the trough level and AUC was 0 .646. The mean AUC of the initial stage and maintenance stage were 4661.8 ng·hr/ml and 2721.1-3072 .7 ng·hr/ml, respectively. In 9 paired observations, the coefficient of variation (CV %) in AUC was significantly smaller than that of trough level (p< 0. 05). The serum potassium (K) with an AUC of 5000-6000 ng·hr/ml was significantly higher than K with an AUC of 2000-3000 ng·hr/ml (p<O. 05).
These results suggest that AUC monitoring is very useful for precise detection of the dosage ajustment in clinical practice.View full abstractDownload PDF (823K) -
Tadahiro SHIKIMP, Hiroshi ISHINO, Yasutoshi HIMENO, Tomoyuki ISHIBE, K ...1993 Volume 24 Issue 4 Pages 571-577
Published: December 31, 1993
Released on J-STAGE: June 28, 2010
DOIhttps://member-cnki-net-s-1416.res.gxlib.org.cn:443/rwt/1416/https/MSYXTLUQPJUB/10.3999/jscpt.24.571JOURNAL FREE ACCESSUlinastatin (urinary trypsin inhibitor) and α1-microglobulin levels in urine samples of 39 dementia patients (Alzheimer-type dementia, 21 cases; vascular dementia, 18 cases) and 14 normal subjects were measured. There was a positive correlation between the ulinastatin and α1-microglobulin levels. Lower scores on the dementia rating scale and activities of daily living were observed in patients with Alzheimer-type dementia but not with vascular dementia, where a lower α1-microglobulin level was registered. However, the ulinastatin level did not correlate with the scores in patients with either Alzheimer-type or vascular dementia. These results indicate that the urinary ar-microglobulin level provides a useful biochemical index of the severity of Alzheimer-type dementia.View full abstractDownload PDF (787K) -
Minae KOBAYASHI, Hisao SHIBATA, Makihiko SUZUKI, Mitsutomo UCHIUMI, Ju ...1993 Volume 24 Issue 4 Pages 579-588
Published: December 31, 1993
Released on J-STAGE: June 28, 2010
DOIhttps://member-cnki-net-s-1416.res.gxlib.org.cn:443/rwt/1416/https/MSYXTLUQPJUB/10.3999/jscpt.24.579JOURNAL FREE ACCESSWe investigated the pharmacokinetic effects of nitrazepam (NZP, 5 mg), a benzodiazepinehypnotic, and rilmazafone hydrochloride (RMZ, 2 mg), a benzodiazepine prodrug with andwithout ethanol (0.7 g/kg body weight).
The study was carried out using the double-blind cross-over blockade design with placeboand vehicle. There were no significant differences in the pharmacokinetic parameters betweenhypnotics alone and hypnotics with ethanol, except for mean residence time (MRT) of RMZ . However, individual variations were found in the serum concentrations of the two hypnotic safter the ethanol consumption as indicated by pharmacokinetic parameters, Cmax and absorption rate. Furthermore, the AUC was lowered in NZP and increased in RMZ in 3 out of8 volunteers with ethanolcombined treatments . These findings were interpreted to reflect thedifferences in metabolic processes between NZP and RMZ; RMZ is metabolized throughdemethylation, while nitro-reduction is involved in the metabolism of NZP.
Regarding RMZ, the serum concentrations of the active metabolites, M-1, M-2, M-Aand M-3 were also measured in two volunteers. Ethanolcombined treatments caused a higherconcentration of M-1 in comparison with RMZ treatment alone. This might be due toblockade of the demethylation process from M-1 to M-2 by ethanol.View full abstractDownload PDF (952K) -
Seiji MIURA, Takashi SHIMIZU, Satoru SHIDA, Yasuhisa ODAGAWA, Yoshikaz ...1993 Volume 24 Issue 4 Pages 589-594
Published: December 31, 1993
Released on J-STAGE: June 28, 2010
DOIhttps://member-cnki-net-s-1416.res.gxlib.org.cn:443/rwt/1416/https/MSYXTLUQPJUB/10.3999/jscpt.24.589JOURNAL FREE ACCESSBisoprolol (Maintate®), a highly β1-selective antagonist, is effective in adults !for a 24-hour period with a daily oral administration 5mg . There are few reports on the use ofbisoprolol in children.
We administered this agent to children with hypertension, angina, or arrythmias aloneor concomitantly.
Thirteen patients aged 5 to 20 years old were recruited for this study . Bisoprolol wasgiven to the patients over 15 years old at a dose of 5mg after breakfast, while to thoseunder 14 years old, a dose of 2. 5mg twice a day was given . The correlation of the blood.concentration at 4 hours after administration and the dose, tmax, t1/2 was compared with thatin adults. Laboratory analyses of hematology and blood chemistry were also conducted beforeand after administration. No abnormal changes in laboratory data were observed.
The correlation o⊥ blood level Y (ng/ml) and the dose per weight X (mg/kg) wassignificant (Y=5.211+223.8X, r= 0.744, p<0.05). The optimal daily dose for children is0. 08mg/kg. Although there was no significant difference in tmax between children and adults, t1/2 in children (5.7 ±1.5hr) was significantly shorter than in adults (8 . 6 ± 1.0hr).
Bisoprolol was clinically effective in 11 patients. However, one patient developed bradycardia due to an overdose. The dose should be adjusted according to the patient's weight .It is, therefore, recommendable to administer bisoprolol twice a day in children.View full abstractDownload PDF (591K) -
Ryuichi KATO1993 Volume 24 Issue 4 Pages 595-602
Published: December 31, 1993
Released on J-STAGE: June 28, 2010
DOIhttps://member-cnki-net-s-1416.res.gxlib.org.cn:443/rwt/1416/https/MSYXTLUQPJUB/10.3999/jscpt.24.595JOURNAL FREE ACCESSOne of the most important areas of the study of clinical pharmacology is the prediction of the clinical dose of new drugs from preclinical data . However, there are few scientific approaches to date. In this report, I therefore attempt to determine some reliable data for the prediction of the clinical dose of new drugs based on clinical data by collecting the nontoxic dose in repeated administration and the clinical dose and the elimination half -life of a variety of orally administered drugs.
The present results clearly showed that, in spite of marked individual differences in the ratios of nontoxic dose and clinical dose, the distribution is unimodal with a median of 30 and 16, respectively, for rats and dogs. The elimination half-life in humans was generally longer than those in rats and dogs, and the ratios were markedly different among drugs, but the ratios were distributed in unimodality with a median of 3.01 and 1.90, respectively, for rats and dogs. There is a clear correlation between the ratio of the nontoxic dose/clinical dose and of human/rat or human/dog for the half-life . Therefore, taking into consideration of species differences in the rate of drug metabolism, I adjusted the nontoxic dose/clinical dose ratio. The new ratio of about 10 for nontoxic dose/clinical dose was obtained irrespective of rats and dogs by using the half-life .
To further evaluate the validity and usefulness of the present data, it is necessary to collect data from many drugs and analyze the AUC (area under plasma concentration -time curve) and the peak plasma concentration in addition to the half -life.View full abstractDownload PDF (1106K)
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