Abstract:
:Comparative pharmacokinetics of vitamin K epoxide reductase antagonists tecarfarin and warfarin were assessed before and after coadministration for 21 days of the CYP450 inhibitor fluconazole in a randomized, open-label, single-center drug interaction study. Twenty healthy adult participants were randomized 1:1 to receive approximately equipotent single oral doses of tecarfarin (50 mg) or warfarin (17.5 mg). Following 7 days of baseline serial blood level collections, each participant received oral fluconazole 400 mg daily for 21 days. A second identical single oral dose of tecarfarin or warfarin was given 14 days after starting fluconazole with serial pharmacokinetic sampling. Key pharmacokinetic parameters C(max), t(max), AUC(0-168), apparent clearance, and t(1/2) demonstrated no tecarfarin-fluconazole interaction but a strong warfarin-fluconazole interaction. The ratio of log-transformed mean AUC(0-168) with versus without fluconazole for tecarfarin was 91.2% (90% confidence interval [CI]: 83.3-99.8) and for racemic warfarin was 213% (90% CI: 202-226). The 90% CI was entirely within the standard 80% to 125% bioequivalence interval for tecarfarin but well outside the bioequivalence interval for warfarin, confirming a clinically significant pharmacokinetic interaction between warfarin and fluconazole. In contrast, tecarfarin pharmacokinetics were apparently unchanged by fluconazole.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Bavisotto LM,Ellis DJ,Milner PG,Combs DL,Irwin I,Canafax DMdoi
10.1177/0091270010370588subject
Has Abstractpub_date
2011-04-01 00:00:00pages
561-74issue
4eissn
0091-2700issn
1552-4604pii
0091270010370588journal_volume
51pub_type
杂志文章,随机对照试验abstract::Tafenoquine is being developed for relapse prevention in Plasmodium vivax malaria. This Phase I, single-blind, randomized, placebo- and active-controlled parallel group study investigated whether tafenoquine at supratherapeutic and therapeutic concentrations prolonged cardiac repolarization in healthy volunteers. Subj...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1002/jcph.302
更新日期:2014-09-01 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::The pharmacokinetics (PK) and safety of single-dose buparlisib (30 mg) were assessed in subjects with mild to severe hepatic impairment (n = 6 each) relative to healthy controls (n = 13). Blood samples were collected until 336 hours postdose and evaluated by liquid chromatography tandem mass spectrometry. PK parameter...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.590
更新日期:2016-03-01 00:00:00
abstract::The frequency of hemodialysis-associated hemorrhage was studied prospectively in two successive, parallel, heparin-controlled studies using epoprostenol (PGI2; average dose, 4.1 ng/kg.min) as the sole antithrombotic agent. Sixty-three patients with active or recently active bleeding underwent 163 hemodialysis treatmen...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1988.tb03222.x
更新日期:1988-09-01 00:00:00
abstract::The pharmacokinetic profile of solifenacin succinate (YM905; Vesicare), a new once-daily bladder-selective muscarinic receptor antagonist, was examined in 2 controlled trials of healthy young men. A single-dose study evaluated 5-, 10-, 20-, 40-, 60-, 80-, and 100-mg doses. A multidose study evaluated 5-, 10-, 20-, and...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/0091270004267592
更新日期:2004-09-01 00:00:00
abstract::A clinical study of bumetanide, a new diuretic, was conducted in outpatients of a cardiology clinic to determine its long-term effectiveness and safety in the treatment of peripheral edema due to congestive heart failure. The drug was administered for at least 24 weeks on a selected group of 34 patients. The patients ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1981.tb05685.x
更新日期:1981-11-01 00:00:00
abstract::In this investigation, the pharmacokinetic and pharmacodynamic properties were determined of multiple doses of sublingual tablets containing either buprenorphine alone or buprenorphine and naloxone. Subjects were experienced opiate users who received escalating doses (4-24 mg) of buprenorphine either alone or in combi...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1177/0091270005284192
更新日期:2006-02-01 00:00:00
abstract::This experiment represents the first time that it has been possible to measure a body fluid compartment by direct means during spaceflight. Based on the results observed in the five crewmen in this study, it is concluded that TBW decreases by 3.4% after 1 to 3 days of exposure to microgravity in the Space Shuttle. Som...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1991.tb03663.x
更新日期:1991-10-01 00:00:00
abstract::The clinical effects of a cardioselective beta-adrenergic blocking drug, acebutolol, were studied in 25 patients with chronic stable angina, using a seven-week single-blind placebo leads to acebutolol (mean dose 913 mg/day) phase followed by 12-week randomized double-blind placebo leads to acebutolol (mean dose 968 mg...
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.tb02688.x
更新日期:1982-08-01 00:00:00
abstract::We report population pharmacokinetic, pharmacodynamic, and pharmacokinetic-safety analyses to support phase II/III dose/regimen selection of alisertib, a selective Aurora A kinase (AAK) inhibitor. Phase I studies in adult cancer patients evaluated dosing on Days 1-7 in 21-day cycles or Days 1-21 in 35-day cycles, with...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.410
更新日期:2015-03-01 00:00:00
abstract::This randomized crossover study in healthy participants assessed pharmacokinetic interactions between telavancin, aztreonam, and piperacillin/tazobactam. Part 1: 11 participants received telavancin 10 mg/kg, aztreonam 2 g, or a combination of telavancin 10 mg/kg+aztreonam 2 g intravenously on 3 separate days. Part 2: ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270009337133
更新日期:2009-07-01 00:00:00
abstract::Ball-and-stick mechanical models, typically associated with chemists, have been helpful in understanding structural problems and the relationship between structure and biologic activity. With progress in computer speed, graphics performance, and software innovation, molecules of biological interest can be subjected to...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1002/j.1552-4604.1993.tb03915.x
更新日期:1993-12-01 00:00:00
abstract::This was a double-blind, placebo-controlled, randomized, parallel, dose-escalation study to assess the pharmacokinetics, platelet response, safety, and tolerability of supratherapeutic doses of eltrombopag (100 mg, 150 mg, and 200 mg once daily) administered for 5 days to 33 healthy adult volunteers. Plasma eltrombopa...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1177/0091270010368677
更新日期:2011-03-01 00:00:00
abstract::Using a sensitive and specific radioimmunoassay the pharmacokinetic disposition of clonidine was determined in hypertensive patients after a single dose and then after 5, 28 and 56 days of chronic dosing with 75 micrograms bd. Following a single dose of clonidine maximal plasma concentrations of 0.34 +/- 0.06 ng/ml we...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1989.tb03335.x
更新日期:1989-04-01 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::A novel, nonscrotal, transdermal delivery system for testosterone therapy has been marketed for treatment of hypogonadal men. The usual dose of this system is two 2.5 mg/day systems applied daily. A new system has been developed that administers a dose of 5 mg/day using a single patch rather than two patches. A random...
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.1552-4604.1998.tb04377.x
更新日期:1998-01-01 00:00:00
abstract::Udenafil, a cyclic guanosine monophosphate-specific phosphodiesterase type 5 inhibitor, has been developed to treat erectile dysfunction. We evaluated the effect of age on the pharmacokinetics and tolerability of udenafil. A single-center, open-label, parallel-group phase 1 study was conducted in healthy adult subject...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.739
更新日期:2016-11-01 00:00:00
abstract::Clinical pharmacology of L-asparaginase was compared by intramuscular and intravenous injections in 12 patients with metastatic cancer or leukemia. Following a single intramuscular injection at the gluteal site of L-asparaginase (10,000 IU/m2), the enzyme appeared in plasma as measured initially at 1 hour, but plateau...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1981.tb01752.x
更新日期:1981-02-01 00:00:00
abstract::Procaterol, a new beta-adrenergic agonist, was tested in two different doses in patients with reversible airway obstruction. Single oral doses of 0.05 or 0.1 mg produce an increase in measured expiratory flow rates, and the peak and duration of action are both dose related. Side effects reported during this one-day st...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1982.tb02669.x
更新日期:1982-05-01 00:00:00
abstract::This study examined warfarin usage for elderly Medicare beneficiaries with atrial fibrillation (AF) who suffered traumatic brain injury (TBI), hip fracture, or torso injuries. Using the 5% Chronic Condition Data Warehouse administrative claims data, this study included fee-for-service Medicare beneficiaries who had a ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.375
更新日期:2015-01-01 00:00:00
abstract::To determine the elimination of high-molecular-weight hydroxyethyl starch (HES, Mw 450,000) in normal subjects, ten volunteers were given 500 ml 6% HES solution by intravenous infusion, and serial blood and urine samples were collected for nonglucose total carbohydrate determination. On the average, 46 and 64 per cent...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1982.tb02164.x
更新日期:1982-04-01 00:00:00
abstract::A bioequivalence study of two oral formulations of 300 mg ranitidine was carried out in 16 healthy volunteers (8 men and 8 women), and the pharmacokinetics in both sexes were compared. There was bioequivalence of both formulations. The terminal half-life of ranitidine was 7% shorter and the oral apparent clearance 10....
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.1552-4604.1996.tb04245.x
更新日期:1996-08-01 00:00:00
abstract::The objective of this study was to determine the absolute oral bioavailability and disposition of omapatrilat. This single-dose, randomized, crossover study of 20 mg intravenous and 50 mg oral [14C]omapatrilat was conducted in 12 healthy male subjects to determine the disposition and oral bioavailability of omapatrila...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/00912700122010726
更新日期:2001-08-01 00:00:00
abstract::These studies were conducted to evaluate the pharmacokinetics of several retinoids after meal consumption or vitamin A supplementation to establish a reference for future assessment of teratogenic risks of retinoid therapeutic agents. In the first study, 36 healthy young female volunteers consumed single meals contain...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1996.tb04253.x
更新日期:1996-09-01 00:00:00
abstract::Sinbaglustat (ACT-519276), a brain-penetrating inhibitor of glucosylceramide synthase and nonlysosomal glucosylceramidase, is developed as a new therapy for lysosomal storage disorders. In the first-in-human study, sinbaglustat was primarily excreted unchanged in urine. This study was conducted to evaluate the effect ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1808
更新日期:2020-12-23 00:00:00
abstract::The absolute bioavailability of oral melatonin tablets was studied in 12 normal healthy volunteers. Subjects were administered, in a randomized crossover fashion, melatonin 2 mg intravenously and 2 and 4 mg orally. Blood was sampled over approximately eight (estimated) half-lives. Both the 2 and the 4 mg oral dosages ...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/00912700022009422
更新日期:2000-07-01 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::A randomized, crossover study was conducted in healthy male volunteers to assess the diurnal variation in the steady-state pharmacokinetics of valproate after multiple 250-mg oral and intravenous infusion doses after an intravenous 750-mg loading dose. Multiple blood samples were collected throughout each 168-hour stu...
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.1552-4604.1994.tb02036.x
更新日期:1994-07-01 00:00:00
abstract::Inhaled glucocorticoids induce therapeutic and adverse systemic effects via the same types of receptors. Analysis of the pharmacokinetic/pharmacodynamic parameters of inhaled glucocorticoids generates a risk-benefit value (RBV). Targeted efficacy with minimal adverse effects helps to quantify an appropriate RBV. High ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1177/0091270003260334
更新日期:2004-01-01 00:00:00
abstract::To study the pharmacokinetics and pharmacodynamics of two intravenous nizatidine dosing regimens, serial plasma concentrations and continuous intragastric pH were monitored simultaneously in 10 subjects with a documented history of duodenal or gastric ulcers. A 24-hour gastric pH profile was characterized for a 300 mg...
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.1552-4604.1989.tb03259.x
更新日期:1989-10-01 00:00:00