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1. |
Lessons From the Frontiers |
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The Journal of Clinical Pharmacology,
Volume 31,
Issue 6,
1991,
Page 491-491
John C. Somberg,
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ISSN:0091-2700
DOI:10.1002/j.1552-4604.1991.tb03724.x
出版商:Blackwell Publishing Ltd
年代:1991
数据来源: WILEY
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2. |
Chronic Benzodiazepine Administration: From the Patient to the Gene |
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The Journal of Clinical Pharmacology,
Volume 31,
Issue 6,
1991,
Page 492-495
Lawrence G. Miller,
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摘要:
Chronic benzodiazepine administration is associated with the development of tolerance and dependence. To evaluate the cellular mechanisms for these phenomena the authors developed a mouse model of chronic benzodiazepine exposure. The benzodiazepine agonists lorazepam, alprazolam, and clonazepam produced tolerance in this system, which was associated in each case with benzodiazepine and GABAAreceptor downregulation. After discontinuation, a syndrome that included increased motor activity and receptor upregulation occurred with each of these compounds. A benzodiazepine antagonist, flumazenil, and an inverse agonist, FG 7142, were associated with receptor upregulation and increased activity during chronic administration. In contrast, a partial agonist (Ro16–6028) did not produce tolerance or receptor changes. Similar results were obtained in a culture system for clonazepam, flumazenil, and FG 7142. The increase in receptor binding after lorazepam discontinuation may be due to enhanced receptor synthesis. Changes in gene expression for GABAAreceptor subunits also occur with chronic lorazepam administration, and they follow alterations in bindin
ISSN:0091-2700
DOI:10.1002/j.1552-4604.1991.tb03725.x
出版商:Blackwell Publishing Ltd
年代:1991
数据来源: WILEY
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3. |
INFORMATION FOR AUTHORS |
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The Journal of Clinical Pharmacology,
Volume 31,
Issue 6,
1991,
Page 495-495
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ISSN:0091-2700
DOI:10.1002/j.1552-4604.1991.tb03726.x
出版商:Blackwell Publishing Ltd
年代:1991
数据来源: WILEY
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4. |
Teaching Courses in Clinical Trial Research Methods |
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The Journal of Clinical Pharmacology,
Volume 31,
Issue 6,
1991,
Page 496-508
Bert Spilker,
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ISSN:0091-2700
DOI:10.1002/j.1552-4604.1991.tb03727.x
出版商:Blackwell Publishing Ltd
年代:1991
数据来源: WILEY
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5. |
The QAU: Friend, Not Foe |
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The Journal of Clinical Pharmacology,
Volume 31,
Issue 6,
1991,
Page 509-511
Alan F. Sewell,
Cheryl D. Spencer,
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ISSN:0091-2700
DOI:10.1002/j.1552-4604.1991.tb03728.x
出版商:Blackwell Publishing Ltd
年代:1991
数据来源: WILEY
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6. |
Lovastatin Therapy in Hypercholesterolemia: Effect on Fibrinogen, Hemorrheologic Parameters, Platelet Activity, and Red Blood Cell Morphology |
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The Journal of Clinical Pharmacology,
Volume 31,
Issue 6,
1991,
Page 512-517
Yitzhak Beigel,
Jacob Fuchs,
Moshe Snir,
Pnina Green,
Yoav Lurie,
Menachem Djaldetti,
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摘要:
The effect of lovastatin therapy on blood rheology was investigated in 26 hypercholesterolemia patients. Treatment with lovastatin was associated with a significant improvement in whole blood filtration time and a tendency toward normalization in red blood cell morphology. A significant increase was observed in fibrinogen level, in ADP‐induced platelet aggregation, in the percentage of “big” platelets, and in platelet count. The viscosity of whole blood and plasma and the percentage of aggregated platelets did not change significantly. The cause for these hemorrheologic changes and their role in influencing the coronary risk of lovastatin‐treated hypercholesterolemia patients should be further inves
ISSN:0091-2700
DOI:10.1002/j.1552-4604.1991.tb03729.x
出版商:Blackwell Publishing Ltd
年代:1991
数据来源: WILEY
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7. |
Effect of Nifedipine on Oxygen Delivery in Patients with Angina Pectoris: Relation Between Blood Viscosity and Hematocrit |
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The Journal of Clinical Pharmacology,
Volume 31,
Issue 6,
1991,
Page 518-520
Tadashi Kato,
Shunki Yoneda,
Toshio Kako,
Masaaki Koketsu,
Takao Fujinami,
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摘要:
The effect of nifedipine on blood viscosity and hematocrit was investigated. Blood was sampled from eight patients with angina pectoris (mean age: 59 ± 8 yr) treated with nifedipine (20–30 mg/day) for 5 months. Using a cone‐plate type viscometer, blood viscosity was determined at the shear rates of 37.5 and 375 sec−1at 37°C. Hematocrit was also measured at the same time. Since the ratio of hematocrit to blood viscosity at a shear rate of 375 sec−1can be considered to reflect oxygen delivery, this ratio (oxygen delivery index) was also calculated. Blood viscosity at a shear rate of 37.5 sec−1was significantly (P<.05) decreased by nifedipine treatment, but hematocrit and the blood viscosity at a shear rate of 375 sec−1were not changed. The oxygen delivery index, however, was significantly (P<.01) increased after the administration of nifedipine. These results suggest that oxygen delivery increased by the treatment with nifedipine and inhibited erythrocyte aggregation by decreasing blood viscosity at l
ISSN:0091-2700
DOI:10.1002/j.1552-4604.1991.tb03730.x
出版商:Blackwell Publishing Ltd
年代:1991
数据来源: WILEY
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8. |
Serum Digoxin Levels Related to Plasma Propafenone Levels During Concomitant Treatment |
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The Journal of Clinical Pharmacology,
Volume 31,
Issue 6,
1991,
Page 521-526
Marie‐Claire Bigot,
Danièle Debruyne,
Laurent Bonnefoy,
Gilles Grollier,
Maurice Moulin,
Jean‐Claude Potier,
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摘要:
Nine patients with supraventricular rhythm disorders were treated during 5‐day periods with different oral doses (300, 450, 600, and 900 mg daily) of propafenone concomitantly to long‐term digoxin treatment. A poor correlation (r =.398;P<.05) was obtained when the difference between the mean digoxin serum level (calculated with the Cmin data determined each of the 5 days) observed during a given propafenone dose and the mean digoxin serum level observed before propafenone treatment, was correlated with the dose of propafenone; but an evident correlation (r =.778;P<.01) was found when the difference in digoxin level was correlated with the plasma propafenone concentration. The propafenone effect of increasing digoxin blood levels was thus concluded to be poorly dose dependent but strongly concentration dependent. The association of propafenone to a long‐term digoxin treatment can be considered with a low risk of toxicity when plasma propafenone concentration does not exceed about 1000 ng/mL. Propafenone plasma levels are unpredictable in view of their wide interindividual variation for a given dose, so their measurement is advised to detect high levels and consequently to prevent a rise in digoxin serum concentrations with the possibility of toxicity. In clinical practice, when propafenone concentration determinations are not readily available, digoxin serum levels at least have to be carefully moni
ISSN:0091-2700
DOI:10.1002/j.1552-4604.1991.tb03731.x
出版商:Blackwell Publishing Ltd
年代:1991
数据来源: WILEY
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9. |
Digoxin Pharmacokinetics and Spirapril, a New Ace Inhibitor |
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The Journal of Clinical Pharmacology,
Volume 31,
Issue 6,
1991,
Page 527-530
Brian F. Johnson,
John Wilson,
Johanna Johnson,
Janeth Flemming,
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摘要:
As concurrent use of digoxin with the novel ACE inhibitor spirapril should be common, potential for spirapril to affect steady‐state digoxin kinetics was studied. Fifteen healthy white male volunteers aged 22–42 and weighing 135–225 lbs took digoxin tablets 0.25 mg every 12 hours for 5 weeks. In crossover design, each also received spirapril or matching placebo capsules during weeks 1 and 2, or 4 and 5. Dosage of spirapril was increased from 12 mg to 48 mg once daily. Spirapril produced no significant effect on mean (±SD) serum digoxin concentration in the steady state, area under curve for 12 hours, peak digoxin level, time to peak, or urinary digoxin excretion over 12 hours. No change in renal or whole body digoxin clearance was seen. Unlike some other cardiovascular drugs, spirapril does not alter steady‐state digoxin kinetics in health
ISSN:0091-2700
DOI:10.1002/j.1552-4604.1991.tb03732.x
出版商:Blackwell Publishing Ltd
年代:1991
数据来源: WILEY
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10. |
Prevention by Pentoxifylline of Transient Ca2+Accumulation and Transglutaminase Activation in Rat Erythrocytes |
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The Journal of Clinical Pharmacology,
Volume 31,
Issue 6,
1991,
Page 531-536
Norbert I. Swislocki,
Joan M. Tierney,
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摘要:
The authors have examined the effects of pentoxifylline, a drug used to improve peripheral blood flow in patients with vascular disorders, on shear‐induced periodic Ca2+entry and its consequences in the rat erythrocyte. To study the effects of periodic Ca2+entry on Ca2+dependent processes, erythrocytes, with and without pentoxifylline, were subjected to rotational shear produced by swirling‐cell suspensions in an isosmotic medium for 5‐second intervals. Pulses of increasing duration from 5–30 seconds promoted increased accumulation of45Ca2+; intermittent 5 sec pulses, at 10‐minute intervals, produced a stepwise accumulation of45Ca2+. Ca2+accumulation was accompanied by elevated Ca2+dependent transglutaminase. Shear induced Ca2+entry and the increase in transglutaminase activity was reduced in cells treated with pentoxifylline. These findings suggest that pentoxifylline can reduce shear induced periodic Ca2+entry that leads to transient activation of Ca2+dependent transglutaminase, accumulation of crosslinked proteins, and loss of erythrocyte defo
ISSN:0091-2700
DOI:10.1002/j.1552-4604.1991.tb03733.x
出版商:Blackwell Publishing Ltd
年代:1991
数据来源: WILEY
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