Abstract：
:The objective of this study was to measure the steady-state cerebrospinal fluid (CSF) concentration of LY450108 and LY451395 (positive modulators of AMPA receptors) in healthy subjects after the administration of 1 mg and 5 mg. Secondary objectives included the evaluation of safety, pharmacokinetics, and steady-state ratio of plasma:CSF concentrations of LY450108 and LY451395 after multiple dosing. This study was an open-label, multiple oral dose study evaluating 1 mg and 5 mg LY450108 and 1 mg and 5 mg LY451395 in 12 (3 subjects per dosing group) healthy subjects, aged 18 to 49 years. Twelve healthy male subjects completed the study. LY450108 and LY451395 were quantifiable in CSF after 1-mg and 5-mg multiple-dose administrations with plasma:CSF ratio of 82:1 and 44:1, respectively. LY450108 and LY451395 1 mg and 5 mg were measured in the CSF. Single and multiple oral doses of LY450108 and LY451395 were determined to be safe and well tolerated in healthy subjects.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Jhee SS,Chappell AS,Zarotsky V,Moran SV,Rosenthal M,Kim E,Chalon S,Toublanc N,Brandt J,Coutant DE,Ereshefsky Ldoi
10.1177/0091270006286899subject
Has Abstractpub_date
2006-04-01 00:00:00pages
424-32issue
4eissn
0091-2700issn
1552-4604pii
46/4/424journal_volume
46pub_type
杂志文章abstract：:Sirolimus (RAPA) and cyclosporine (CsA) are immunosuppressive compounds that are being used concomitantly in renal transplant patients. Both drugs are dosed orally, have common intestinal and hepatic metabolism and intestinal transport mechanisms, and thus offer potential for pharmacokinetic drug interactions. A singl...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/0091270003257227
更新日期：2003-10-01 00:00:00
abstract：:L- and T-type voltage-dependent transmembrane calcium channels are important for normal functioning of the cardiovascular system. T-type channels are a heterogeneous group, and have physiologic and pathophysiologic relevance in a number of organ systems, including the heart and central nervous system. They appear to b...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/j.1552-4604.1998.tb04804.x
更新日期：1998-08-01 00:00:00
abstract：:Argatroban, a direct thrombin inhibitor, is metabolized in vitro by CYP3A4/5 and therefore may be susceptible to clinically relevant CYP3A drug interactions. The effect of erythromycin, a potent CYP3A4/5 inhibitor, on the pharmacokinetics and pharmacodynamics of argatroban was evaluated in 14 healthy male volunteers i...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：
更新日期：1999-05-01 00:00:00
abstract：:Nineteenth century ophthalmology, characterized by significant gains in diagnostic techniques, provided the basis for great advancements in treatment during the 20th century. Drug therapy at the turn of the century was empiric, palliative, and often toxic. The development of ocular pharmacology during the 20th century...
journal_title：Journal of clinical pharmacology
pub_type： 历史文章,杂志文章
doi：10.1177/00912700022009710
更新日期：2000-09-01 00:00:00
abstract：:Everolimus is an immunosuppressant intended for use with cyclosporine in acute-rejection prophylaxis following organ transplantation. The possibility of a drug interaction of cyclosporine on everolimus was assessed. In this randomized, two-period, crossover study, 24 healthy subjects received a single oral dose of 2 m...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/0091270002042001011
更新日期：2002-01-01 00:00:00
abstract：:In many industrialized nations, the elderly comprise the fastest growing subpopulation and constitute an increasing proportion of the total population compared to other age groups. The elderly use a disproportionately larger amount of health care resources since they experience a higher incidence of disease-related mo...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1999-11-01 00:00:00
abstract：:Sixteen essential hypertensive patients were entered into a protocol assessing the effect of Spirapril, an angiotensin-converting enzyme (ACE) inhibitor, on blood pressure, the renin-aldosterone system, and renal function. Specifically monitored before, during 6 weeks, and 6 months of Spirapril therapy were plasma ren...
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：:Inhibition of ex vivo arachidonic acid (AA)-induced aggregation is a biomarker for the isotype selectivity of cyclooxygenase (COX) inhibitors since platelets express COX-1 but not COX-2. At low concentrations, there is broad inter- and intrasubject variability in AA-induced aggregation of platelets ex vivo. This study...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270003257216
更新日期：2003-09-01 00:00:00
abstract：:A mechanistic drug-disease model was developed on the basis of a previously published integrated glucose-insulin model by Jauslin et al. A glucokinase activator was used as a test compound to evaluate the model's ability to identify a drug's mechanism of action and estimate its effects on glucose and insulin profiles ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270011422231
更新日期：2012-12-01 00:00:00
abstract：:HMR1031 is a potent and specific antagonist of the integrin VLA-4 (alpha4beta1) binding to vascular cell adhesion molecule-1 (VCAM-1) and fibronectin. HMR1031 is an inhaled drug being developed for the treatment of asthma using an Ultrahaler dry-powder inhalation device. A pharmacoscintigraphic study of HMR1031 sugges...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/0091270003258172
更新日期：2003-12-01 00:00:00
abstract：:This 30-center, randomized, double-blind, placebo-controlled, parallel-group study was designed to (1) establish that 6.25 mg of hydrochlorothiazide (HCTZ) given once daily with 5 mg of bisoprolol fumarate can contribute to antihypertensive effectiveness in patients with stage I and stage II (mild to moderate) systemi...
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.1552-4604.1995.tb05009.x
更新日期：1995-02-01 00:00:00
abstract：:The aim of this study was to apply individualized, physiologically-based pharmacokinetic (iPBPK-R) modeling of 14 CO2 production rates measured by the erythromycin breath test (ERMBT) to characterize the effect of hemodialysis on the function of nonrenal clearance pathways in patients with end-stage renal disease (ESR...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1818
更新日期：2021-01-18 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：:The pharmacokinetics and safety of a single oral dose of 200-mg plant-derived pharmaceutical formulation of highly purified cannabidiol (CBD) in oral solution (Epidiolex in the United States; 100 mg/mL) were assessed in subjects with mild to severe hepatic impairment (n = 8 each for mild and moderate, n = 6 for sever...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1002/jcph.1412
更新日期：2019-08-01 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：:Fosamprenavir (FPV) is the phosphate ester prodrug of the HIV-1 protease inhibitor amprenavir (APV). A pediatric population pharmacokinetic model for APV was developed and simulation was used to identify dosing regimens for pediatric patients receiving FPV in combination with ritonavir (RTV) which resulted in concentr...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.205
更新日期：2014-02-01 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：:Pharmacokinetics (PK) of doripenem was determined during high volume hemodiafiltration (HVHDF) in patients with septic shock. A single 500 mg dose of doripenem was administered as a 1 hour infusion during HVHDF to 9 patients. Arterial blood samples were collected before and at 30 or 60 minute intervals over 8 hours (1...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/jcph.432
更新日期：2015-04-01 00:00:00
abstract：:A four-week comparison of protriptyline 10 mg three times a day and perphenazine 2 mg three times a day, alone and in combination, and a placebo in a group of nonpsychotic depressed outpatients showed no significant differences among any of the treatment groups after both two and four weeks, and a slight trend in favo...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1975.tb02382.x
更新日期：1975-08-01 00:00:00
abstract：:The isoproterenol sensitivity (dose-response curve) and the total body clearance of propranolol were measured in 80 men including 15 normal subjects and 65 essential hypertensive patients (20 borderline and 45 permanent hypertensives). The critical dose of isoproterenol was found to be directly correlated to weight (P...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1976.tb01514.x
更新日期：1976-04-01 00:00:00
abstract：:The pharmacokinetic characteristics of a slow-release formulation of clonidine (150 micrograms) were compared with those of a conventional formulation (75 micrograms) after acute and chronic (2 week) administration to 12 hypertensive subjects. The Tmax of the slow-release formulation was significantly later than for t...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1992.tb03858.x
更新日期：1992-05-01 00:00:00
abstract：:The hypotensive efficacy of labetalol was evaluated in 29 patients with essential hypertension in a single-blind dose ranging study. After a two-week period of placebo treatment, labetalol was given in oral doses of 0.6 g/d, 0.8 g/d, and 0.8 g/d combined with 25-50 mg/d of hydrochlorothiazide. Each regimen lasted four...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1986.tb03536.x
更新日期：1986-05-01 00:00:00
abstract：:The pharmacokinetics, pharmacodynamics, and safety of fosinopril sodium (SQ 28,555), a new orally active angiotensin-converting enzyme (ACE) inhibitor, was evaluated in 73 healthy men in two separate studies. In study I, doses ranging from 10 to 640 mg were administered once daily for 3 days to seven groups of five su...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1991.tb01887.x
更新日期：1991-01-01 00:00:00
abstract：:The purpose of this open-label, parallel-group study was to investigate the effect of severe renal impairment on the pharmacokinetics (PK), tolerability, and safety of clazosentan, an intravenous endothelin receptor antagonist. Clazosentan was administered as a continuous intravenous infusion of 1 mg/h for a period of...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270010368975
更新日期：2011-03-01 00:00:00
abstract：:Magnesium sulfate is the anticonvulsant of choice for eclampsia prophylaxis and treatment; however, the recommended dosing regimens are costly and cumbersome and can be administered only by skilled health professionals. The objectives of this study were to develop a robust exposure-response model for the relationship ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1448
更新日期：2019-11-01 00:00:00
abstract：:DS-1040, a low-molecular-weight imidazole derivative, inhibits the enzymatic activity of thrombin-activatable fibrinolysis inhibitor (TAFIa), enhancing endogenous tissue plasminogen activator-triggered fibrinolysis. This first-in-human, randomized, placebo-controlled, phase 1 study evaluated the safety, pharmacokineti...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.1474
更新日期：2019-12-01 00:00:00
abstract：:Aminoglycosides have become an indispensable component in the armamentarium against serious gram-negative infections. In spite of the availability of effective guidelines for prevention, the frequency of toxic side effects associated with aminoglycoside therapy is an impetus for the substitution of safer and equally e...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/j.1552-4604.1988.tb03109.x
更新日期：1988-10-01 00:00:00
abstract：:The pharmacokinetics and pharmacodynamics of intravenous famotidine were evaluated in 10 infants ranging from 5 to 19 days of age who had a therapeutic indication for the prophylactic treatment of stress ulceration. After a 0.5-mg/kg infusion of famotidine, timed serum (n = 6), urine (24-hour collection), and repeated...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1998-12-01 00:00:00
abstract：:The authors investigated the pharmacokinetics of mycophenolic acid over 1 year in 8 Caucasian women undergoing islet cell transplantation. Total mycophenolic acid AUC(0-12) mcg x h/mL before day 60 was 62.1-67.8, declining to 33.6-64.7 thereafter (P = .61). Median total trough concentrations were 1.16-2.90 mcg/mL. Unb...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270005278599
更新日期：2005-08-01 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
