Abstract：
:Six obese (mean weight 92 kg) and five normal (60 kg) subjects received 2 mg diazepam nightly for 30 nights. Determination of diazepam and desmethyldiazepam plasma concentrations during the dosing period and for a withdrawal period indicated that accumulation half-life for both diazepam (7.8 days in obese vs. 3.1 days in normal subjects, P less than 0.05) and desmethyldiazepam (30.3 vs. 7.2 days, P less than 0.05) was markedly prolonged in obese subjects. However, mean steady-state plasma concentrations of diazepam (68 vs. 67 ng/ml) and desmethyldiazepam (156 vs. 91 ng/ml) did not significantly differ between groups. To determine the basis for this delay in accumulation in obese subjects, single-dose pharmacokinetics of diazepam and desmethyldiazepam were determined. Diazepam elimination half-life was greatly prolonged in the obese subjects (82 vs. 32 hours, P less than 0.005), with no change in total metabolic clearance (32 vs. 26 ml/min). Instead, a large increase in volume of distribution (228 vs. 70 liters, P less than 0.01) was the reason for prolongation of the elimination half-life. Similarly for desmethyldiazepam, elimination half-life was prolonged in obese subjects (130 vs. 56 hours, P less than 0.01), without a change in total metabolic clearance (13.7 vs. 19.2 ml/min), due to increased volume of distribution (151 vs. 73 liters, P less than 0.01). During chronic dosing with diazepam, obese patients may experience a much slower onset of maximal drug effect compared to normal-weight patients because of the greatly delayed accumulation of diazepam and desmethyldiazepam.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Abernethy DR,Greenblatt DJ,Divoll M,Shader RIdoi
10.1002/j.1552-4604.1983.tb02750.xsubject
Has Abstractpub_date
1983-08-01 00:00:00pages
369-76issue
8-9eissn
0091-2700issn
1552-4604journal_volume
23pub_type
杂志文章abstract：:The centrally acting agents are one of several differing classes of drugs now available for antihypertensive therapy. The availability of newer pharmacologic classes, including the beta-blockers, alpha-blockers. ACE inhibitors and calcium channel blockers, has resulted in a relative decline in the use of the centrally...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/j.1552-4604.1989.tb03387.x
更新日期：1989-07-01 00:00:00
abstract：:Chemotherapy-induced nausea and vomiting (CINV) is a common treatment-related adverse event that negatively impacts the quality of life of cancer patients. During pediatric drug development, extrapolation of efficacy from adult to pediatric populations is a pathway that can minimize the exposure of children to unneces...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
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abstract：:The effect of epoprostenol on the pharmacokinetics of furosemide was investigated in 23 patients with end-stage congestive heart failure (CHF) receiving conventional therapy alone or conventional therapy plus epoprostenol. Estimates of the apparent oral clearance, volume of distribution, and absorption rate constant f...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1996.tb04196.x
更新日期：1996-03-01 00:00:00
abstract：:Approximately equianalgesic oral doses of codeine, an oxycodone compound resembling Percodan, and pentazocine were compared for adverse effects in a double-blind, randomized study of four doses of each drug given over two days to 247 postsurgical patients with pain. Placebo and parenteral morphine were also treated as...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/j.1552-4604.1981.tb01724.x
更新日期：1981-01-01 00:00:00
abstract：:The electrocardiographic (ECG) effects of rivastigmine treatment were assessed in mild to moderately severe Alzheimer's disease (AD) by analysis of four 26-week, double-blind, multicenter, placebo-controlled, phase III clinical trials. Of an initial 2791 patients, 77% completed treatment. Seventy-one percent required ...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1177/00912700222011490
更新日期：2002-05-01 00:00:00
abstract：:The objective of this study was to establish effects of inhaled loxapine on the QTc interval in this randomized, placebo-controlled, double-blind crossover study. Forty-eight healthy volunteers received a single inhaled placebo or 10 mg loxapine. Plasma concentrations of loxapine increased with a median Tmax of 1 minu...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.257
更新日期：2014-06-01 00:00:00
abstract：:In patients with renal insufficiency, dose adjustments based on creatinine clearance and body weight have been a component of imipenem dosage instructions. The objective of the current analysis was to provide revised dosing recommendations by evaluating the impact of creatinine clearance and body weight on the pharmac...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/jcph.1356
更新日期：2019-05-01 00:00:00
abstract：:The need for clinical pharmacology in research and education, drug development, and health care delivery is well known. However, a current profile of those working in the field is not available. The ACCP authorized a survey of clinical pharmacologists to provide such a profile. Members of the ACCP or ASCPT were solici...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1989.tb03404.x
更新日期：1989-08-01 00:00:00
abstract：:A single evening dose of a clonidine-chlorthalidone combination (Combipres) was compared with the usual twice-daily schedule in 11 patients with essential hypertension. No significant difference was found between the blood pressures recorded on the two regimens or between morning and afternoon pressures on the once-da...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1980.tb01695.x
更新日期：1980-04-01 00:00:00
abstract：:Vildagliptin is a potent and selective dipeptidyl peptidase IV inhibitor in development for the treatment of type 2 diabetes that improves glycemic control by enhancing alpha- and beta-cell responsiveness to glucose. Two open-label, single-dose, randomized, crossover studies in healthy subjects (ages 18-45 years) inve...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270007304313
更新日期：2007-09-01 00:00:00
abstract：:In most Wuchereria bancrofti and Brugia malayi infections, the microfilaria are found in the blood in greatest number between 10 p.m. and 2 a.m., indicating that chronotherapy may be beneficial in treating such infections. This study reports the influence of time of administration on the pharmacokinetics of diethylcar...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/00912700222011247
更新日期：2002-03-01 00:00:00
abstract：:Propafenone and its 5-hydroxy metabolite exhibit different electrophysiological properties. Objectives of the CAQ-PAF study were (1) to develop a strategy favoring propafenone instead of 5-hydroxypropafenone in plasma following oral administration of propafenone and (2) to evaluate the potential of low-dose quinidine ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270011399574
更新日期：2012-02-01 00:00:00
abstract：:Atrial fibrillation is very common in the United States. After a search of Medline, EMBASE, and CINAHL, 4 trials evaluating inhibitors of the renin-angiotensin system were identified for prevention of new-onset atrial fibrillation, facilitation of electrical cardioversion of atrial fibrillation, and prevention of atri...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,meta分析
doi：10.1177/0091270005283284
更新日期：2006-01-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1991.tb01888.x
更新日期：1991-01-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/009127001773744297
更新日期：2001-07-01 00:00:00
abstract：:Data from over 1000 patients with rheumatoid arthritis who received tolmetin sodium in double-blind and open studies have been pooled to assess long-term efficacy and safety. Duration of the studies was 12 weeks to 48 months. Mean age of patients was 54 years; ratio of males to females was 1:3. The results showed that...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1983.tb02739.x
更新日期：1983-07-01 00:00:00
abstract：:The therapeutic and biochemical effects of two commonly employed diuretic preparations were compared in a double-blind fashion in 32 patients with congestive heart failure. At the doses employed, furosemide and a fixed combination of spironolactone and hydrochlothiazide maintained control of the clinical manifestation...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
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更新日期：1977-07-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1993.tb04668.x
更新日期：1993-04-01 00:00:00
abstract：:The objective of this study was to investigate the influence of food on the pharmacokinetics of tolterodine, its active 5-hydroxymethyl metabolite (5-HM), and exposure to the active moiety (sum of unbound tolterodine + 5-HM) in healthy volunteers. Serum concentrations of tolterodine and 5-HM were measured for up to 12...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/00912700122010113
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abstract：:Epoxieicosatrienoic acids (EETs) play a protective role against damaging processes in the kidney. We have assessed the effect of polymorphisms in EETs-producing enzymes (CYP2C8 and CYP2J2) and other proteins involved in calcineurin inhibitors (CNIs) disposition (CYP3A4, CYP3A5, and ABCB1) on graft function and clinica...
journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/j.1552-4604.1981.tb05671.x
更新日期：1981-11-01 00:00:00
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journal_title：Journal of clinical pharmacology
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更新日期：2019-01-01 00:00:00
abstract：:Quazepam is a new benzodiazepine that may provide good hypnotic action with negligible effect on motor coordination or respiration. Sleep laboratory studies on human volunteers have shown quazepam 15 mg to be an effective hypnotic dose, with the 30-mg dose being optimal. At these doses, there was no deterioration of m...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1987.tb03020.x
更新日期：1987-04-01 00:00:00
abstract：:Moxifloxacin is used in thorough QT studies to assess sensitivity for detection of an increase in QTc. Moxifloxacin is usually over-encapsulated for blinding. However, there is concern that over-encapsulation alters its pharmacokinetics. In a 4-arm, randomized crossover study, 22 volunteers received over-encapsulated ...
journal_title：Journal of clinical pharmacology
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更新日期：2010-11-01 00:00:00
abstract：:PRX-00023 is a novel, nonazapirone 5-HT1A agonist in clinical development for treatment of affective disorders. The objectives of the initial clinical phase I studies (a single ascending dose study and multiple dose-ascending and high-dose titration studies) were to measure the pharmacokinetics, pharmacodynamic (neuro...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270007300953
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abstract：:The objective of this study was to establish effects of liraglutide on the QTc interval. In this randomized, placebo-controlled, double-blind crossover study, 51 healthy participants were administered placebo, 0.6, 1.2, and 1.8 mg liraglutide once daily for 7 days each. Electrocardiograms were recorded periodically ov...
journal_title：Journal of clinical pharmacology
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更新日期：2009-11-01 00:00:00
abstract：:The influence of food on the bioavailability of trimoprostil , a new antiulcer prostaglandin E2 derivative, was investigated in healthy male volunteers in four separate studies. Doses of 0.75, 1.5, and 3.0 mg were administered orally in both the presence and absence of food followed by serial blood sampling through 24...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1984.tb01830.x
更新日期：1984-04-01 00:00:00
abstract：:The possible effect of oral flecainide acetate on steady-state digoxin levels was assessed in 15 healthy men. Each volunteer received digoxin 0.25 mg daily (8 AM) for 22 consecutive days and flecainide 200 mg bid (8 AM and 8 PM) on days 11 through 15. Plasma digoxin and flecainide levels were measured by radioimmunoas...
journal_title：Journal of clinical pharmacology
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abstract：:Controlled-onset extended-release verapamil (COER-V) is designed so drug concentrations rise sharply in the early morning to coincide with the peak incidence of cardiovascular events. The primary objective of this study was to compare the diurnal pattern of forearm vascular resistance (FVR) between hypertensives and n...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-12-01 00:00:00
