Abstract：
:This report describes the first evaluation in humans of Ro 41-3696. Based on its preclinical profile, Ro 41-3696, a nonbenzodiazepine partial agonist at the benzodiazepine receptor, offers promising perspectives as an innovative hypnotic drug in that it does not exhibit most of the disadvantages associated with full agonists. Single oral doses of 0.1, 0.3, 1.0, 3.0, 10, and 30 mg were administered sequentially to six groups of six healthy male volunteers in a placebo-controlled, double-blind design. Tolerability was assessed and pharmacokinetic and pharmacodynamic measurements were conducted during a period of 28 hours after drug intake. Ro 41-3696 was well tolerated at all doses, causing no clinically relevant changes in vital signs or laboratory parameters. At doses of 10 and 30 mg there were signs of unsteady gait, indicating a central nervous system depressant effect. Pharmacokinetic analyses revealed that Ro 41-3696 was absorbed and eliminated rapidly (tmax = approximately 1 hour; t1/2 = approximately 4 hours). At all times plasma levels of Ro 41-3290, the desethylated derivative of Ro 41-3696, were higher than those of the parent drug (tmax and t1/2 values = approximately 2 and 8 hours, respectively). Area under the curve (AUC) data indicated dose-proportional pharmacokinetics for both Ro 41-3696 and Ro 41-3290. Performance in both a tracking and a memory search test was significantly affected by doses of 10 and 30 mg, and long-term memory, as assessed by a word learning and recall test, was slightly impaired at these doses. The results of this study support the initiation of therapeutic efficacy studies with Ro 41-3696 in doses up to approximately 5 mg and further exploration of the characteristics of Ro 41-3290.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Dingemanse J,Bury M,Roncari G,Zell M,Gieschke R,Gaillard AW,Odink J,van Brummelen Pdoi
10.1002/j.1552-4604.1995.tb04126.xsubject
Has Abstractpub_date
1995-08-01 00:00:00pages
821-9issue
8eissn
0091-2700issn
1552-4604journal_volume
35pub_type
临床试验,杂志文章,随机对照试验abstract：:In 1989, the second-year medical school pharmacology course at New York Medical College was revised to help improve student and faculty morale, improve scores on class exams and the U.S. Medical Licensing Examination (USMLE), and encourage more active student participation in the course. Rather than incorporating new ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1177/00912700022008667
更新日期：2000-01-01 00:00:00
abstract：:In a double-blind sequential trial, the influence of transdermal electrical nerve stimulation (TENS) was studied in patients who were treated with total infusions of metoclopramide 3.5 mg/kg to counter the emetic action of cisplatin 60-90 mg/m2. Transdermal electrical nerve stimulation further reduced the emetic episo...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1986.tb02918.x
更新日期：1986-02-01 00:00:00
abstract：:The pathophysiology of poliomyelitis and the recognition of the "post-polio syndrome" suggest that susceptibility to muscle relaxants of patients previously affected by this disease, may be altered. We compared the effects of d-tubocurarine (dTc), pancuronium (P), and gallamine (G) on two pediatric surgical patient gr...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1990.tb03458.x
更新日期：1990-02-01 00:00:00
abstract：:The effect of bilastine on cardiac repolarization was studied in 30 healthy participants during a multiple-dose, triple-dummy, crossover, thorough QT study that included 5 arms: placebo, active control (400 mg moxifloxacin), bilastine at therapeutic and supratherapeutic doses (20 mg and 100 mg once daily, respectively...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/0091270011407191
更新日期：2012-06-01 00:00:00
abstract：:A total of 175 physicians were surveyed by questionnaire before a Clinical Pharmacology Consult Service was started. Of those that responded, 72% thought the service would be helpful, although 40% said they would use the service no more than once a month. Most physicians (75%) preferred self-initiated consultations to...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1988.tb03096.x
更新日期：1988-01-01 00:00:00
abstract：:CBER's philosophy partners with the sponsor's philosophy in the development of electronic dossiers. Based on the experience gained from a number of dossiers, CBER has established a standard management paradigm and imaging platform by which the review of radiographs has been facilitated. ...
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：:Liraglutide is a once-daily glucagon-like peptide-1 analogue being developed for the treatment of type 2 diabetes. The aim of this study was to investigate the effect of age and gender on the pharmacokinetics of liraglutide. Eight male and 8 female subjects were recruited from an 18- to 45-year-old group and an over-6...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270006288215
更新日期：2006-06-01 00:00:00
abstract：:Tissue pharmacokinetics and plasma protein binding of colistin have not been described in humans in vivo. Colistin concentrations in plasma, muscle, and subcutis of healthy volunteers were measured by microdialysis after a single dose of 2.5 million IU of colistin methanesulfonate. In vitro microdialysis experiments a...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/jcph.419
更新日期：2015-04-01 00:00:00
abstract：:Because of the key role blood viscosity plays in the regulation of blood pressure (BP) and the hemorheological effects of pentoxifylline (PTX), this study was conducted to evaluate whether PTX can reduce BP when added to captopril in patients with stage 1 hypertension. In this randomized clinical trial 62 patients wit...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1516
更新日期：2020-02-01 00:00:00
abstract：:Inflammatory conditions, such as rheumatoid arthritis, reduce response to calcium channel and beta-adrenergic antagonists but not the angiotensin II type 1 receptor (AT(1)R) antagonist valsartan. Inflammation also reduces clearance of some drugs or active metabolite, thereby reducing response. Active (n = 14) and cont...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270006292163
更新日期：2006-11-01 00:00:00
abstract：:In this study, the authors assessed the bioequivalence of two fluoxetine tablet formulations in 24 healthy volunteers of both sexes who received a single 20 mg dose of each fluoxetine formulation, and a new sensitive method for the quantification of fluoxetine and norfluoxetine in human plasma was developed. The study...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/00912709922011827
更新日期：1999-10-01 00:00:00
abstract：:It is well known that the CYP2C19 genetic polymorphism influences the pharmacokinetics and pharmacodynamics of proton pump inhibitors (PPIs), but no report has addressed the effects on ilaprazole, a newly developed PPI. To investigate the effects of the CYP2C19 genetic polymorphism on the disposition and pharmacodynam...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270011408611
更新日期：2012-07-01 00:00:00
abstract：:The analgesic activity of buprenorphine was monitored versus that of morphine in a double-blind, randomized, multiple-dose, parallel-design study involving 97 postsurgical patients. Patients could receive intramuscular injections of either buprenorphine (0.3, o.45, or 0.6 mg) or morphine (10, 15, or 20 mg) every 3 or ...
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.1552-4604.1982.tb02158.x
更新日期：1982-04-01 00:00:00
abstract：:This study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of a novel depot formulation of abarelix, a new gonadotropin-releasing hormone (GnRH) antagonist. This was an open-label, sequential two-phase study in healthy male subjects ages 50 to 75. Subjects received a single intramuscular (IM) do...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270004264920
更新日期：2004-05-01 00:00:00
abstract：:To test the effects of fluvastatin on low-density lipoprotein (LDL) receptor activity in patients with heterozygous familial hypercholesterolemia, the authors measured LDL receptor activity in stimulated T-lymphocytes prepared from 34 patients before and after treatment with 40 mg fluvastatin daily for 12 weeks. Maxim...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/00912700022009008
更新日期：2000-04-01 00:00:00
abstract：:This study was undertaken to determine the relationship of serum ACD levels to dosage in a group of patients who had been seizure free for at least two years. It demonstrated that some patients remain completely seizure free with DPH and/or phenobarbital serum concentrations which are well below the reported "optimal"...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1976.tb01491.x
更新日期：1976-01-01 00:00:00
abstract：:The hydrochlorothiazide component of Maxzide (Lederle Laboratories, Pearl River, NY) has been shown to be more bioavailable than the hydrochlorothiazide component of Dyazide (Smith, Kline and French Laboratories, Philadelphia, PA). The authors compared the antihypertensive effectiveness of a half-tablet of Maxzide (25...
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.1552-4604.1990.tb03632.x
更新日期：1990-08-01 00:00:00
abstract：:A decrease in dietary protein intake lowers the clearance of a number of substances excreted principally by the kidney including uric acid and oxypurinol, the major metabolite of allopurinol. We studied the kinetics of uric acid and oxypurinol in seven healthy volunteers on a normal protein diet (2600 calories; 100 g ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1989.tb03239.x
更新日期：1989-01-01 00:00:00
abstract：:Using the hot plate test, the potency and mechanism of the analgesic activity of levonantradol was studied in mice. Levonantradol is 10 to 30 times more potent than morphine; the antinociception can be only partially blocked by naloxone. Similar limited antagonism by cholinergics indicates possible opiodergic mechanis...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1981.tb02611.x
更新日期：1981-08-01 00:00:00
abstract：:Intravenous administration of acetaminophen is an alternative to the oral and rectal routes, which may be contraindicated in particular clinical settings. This randomized, placebo-controlled study of intravenous acetaminophen (Ofirmev, Mallinckrodt Pharmaceuticals, Bedminster, New Jersey) in neonate and infant patient...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1508
更新日期：2020-01-01 00:00:00
abstract：:A double-blind controlled trial was carried out to compare the effects of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), and placebo on cholesterol and triglyceride levels in patients with endogenous hypertriglyceridemias. The dose of both bile acids was four 150-mg capsules day. Total serum cholesterol le...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1981.tb01746.x
更新日期：1981-10-01 00:00:00
abstract：:A physiologically based pharmacokinetic model (PBPK) was built for citalopram using Simcyp-based absorption, distribution, metabolism, and excretion simulator. Various physicochemical properties of citalopram were obtained from the published literature. The in vitro-in vivo extrapolation method was used to predict cle...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1541
更新日期：2020-04-01 00:00:00
abstract：:The safety and efficacy of step-one therapy with enalapril, a new angiotensin-converting enzyme inhibitor, and metoprolol were compared in a double-blind, multicenter study involving 150 patients who had mild to moderate essential hypertension. After a four-week period of placebo run-in, therapy was initiated with twi...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1987.tb03050.x
更新日期：1987-07-01 00:00:00
abstract：:The drug-drug and drug-food interactions between tenofovir DF and didanosine EC were evaluated in 2 pharmacokinetic studies in healthy adult subjects. When 400 mg was dosed with tenofovir DF, mean didanosine AUC was increased by 44% to 60% following fasted or fed administration. Staggered coadministration (2 hour, fas...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270005281351
更新日期：2005-12-01 00:00:00
abstract：:The efficacy and tolerability of aminoglutethimide for the treatment of Cushing's syndrome was assessed in 66 cases three of which are described in the present paper. Aminoglutethimide provided palliation from the signs and symptoms of hypercorticism in 13 of 21 patients with metastatic adrenocortical carcinoma and fo...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1976.tb01504.x
更新日期：1976-11-01 00:00:00
abstract：:Apomorphine-induced vomiting is often used for preclinical efficacy testing of putative antiemetics in normal volunteers. The usual technique of individual intravenous titration for finding the threshold emitic dose of apomorphine in each subject is slow and tedious. We used a uniform dose of 0.05 mg/kg apomorphine gi...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1978.tb02427.x
更新日期：1978-02-01 00:00:00
abstract：:UCN-01 is a protein kinase inhibitor under development as a novel anticancer drug. The initial pharmacologic features in patients were not predicted from preclinical experiments. The distribution volume and the systemic clearance were much lower than those in experimental animals (mice, rats, and dogs), and the elimin...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1177/0091270005274549
更新日期：2005-04-01 00:00:00
abstract：:Numerous physiologic variations, including urinary protein excretion, low serum albumin concentrations, and reductions in kidney function (clearance), exist in patients with glomerulonephritis. These factors could alter the disposition of numerous drugs. The purpose of the current article was to review the influence o...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1177/0091270011413895
更新日期：2012-01-01 00:00:00
abstract：:A new polymeric matrix technology provides a sustained-release formulation of diltiazem hydrochloride (diltiazem SR) suitable for once-daily therapy. The efficacy and safety of diltiazem SR were evaluated in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. After a single-blind, placeb...
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：10.1002/j.1552-4604.1992.tb03887.x
更新日期：1992-09-01 00:00:00
abstract：:Concentrations in breast milk of medications used during general anesthesia were measured to determine whether interruption of breast-feeding was indicated. Breast milk and maternal blood samples were obtained from nine women undergoing tubal sterilization under general anesthesia. Concentrations of methohexital, mepe...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1997.tb04780.x
更新日期：1997-03-01 00:00:00
