Abstract：
:Amiodarone is a unique antiarrhythmic agent originally developed as a vasodilator. Classified electrophysiologically as a Type III antiarrhythmic, it also has both nonspecific antisympathetic and direct, fast channel-membrane effects. Hemodynamic effects of orally administered amiodarone (a negative inotropic agent) are usually negligible, and are usually compensated for by induced vasodilation. Effects on thyroid and hepatic function may help to explain some of the unique pharmacologic as well as toxicologic effects of the drug. Amiodarone is poorly bioavailable (20-80%) and undergoes extensive enterohepatic circulation before entry into a central compartment. The principal metabolite, mono-n-desethyl amiodarone is also an antiarrhythmic. From this central compartment, it undergoes extensive tissue distribution (exceptionally high tissue/plasma partition coefficients). The distribution half-life of amiodarone out of the central compartment to peripheral and deep tissue compartments (t1/2 alpha) may be as short as 4 hours. The terminal half-life (t1/2 beta) is both long and variable (9-77 days) secondary to the slow mobilization of the lipophilic medication out of (primarily) adipocytes. A pharmacokinetically based loading scheme is described, and data suggesting a role for routine amiodarone plasma levels are presented.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Freedman MD,Somberg JCdoi
10.1002/j.1552-4604.1991.tb03673.xsubject
Has Abstractpub_date
1991-11-01 00:00:00pages
1061-9issue
11eissn
0091-2700issn
1552-4604journal_volume
31pub_type
杂志文章,评审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：:Coronary heart disease, hypertension, and dyslipidemia are highly prevalent and commonly coexist in people who are middle-aged and older. Previous data suggested that lowering cholesterol concentrations in individuals at high risk of cardiovascular disease improved clinical outcomes. Xuezhikang, a partial extract of r...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1177/0091270009337509
更新日期：2009-08-01 00:00:00
abstract：:The overall response rate (ORR) is a largely adopted outcome measure in early-phase oncology trials. ORR is highly relevant in cancer drug development at the time of deciding whether to move to confirmatory phase 3 trials; moreover, ORR is gaining increasing relevance in fast-track registration procedures. No systemat...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1790
更新日期：2020-11-26 00:00:00
abstract：:Aprepitant or its prodrug fosaprepitant, in combination with a corticosteroid and a 5-HT(3) receptor antagonist, are used to prevent chemotherapy-induced nausea and vomiting. This study evaluated the effect of fosaprepitant 150 mg on CYP3A4 metabolism. Fosaprepitant 150 mg has been submitted to regulatory agencies for...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270010387792
更新日期：2011-12-01 00:00:00
abstract：:This study aimed to investigate a food effect on the bio-availability of modified-release (MR) trimetazidine tablets in 36 healthy volunteers. Trimetazidine, an anti-ischemic drug, protects the myocardial cell from the harmful effects of ischemia. The authors investigated the effect of being under a fasting or fed sta...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270011422813
更新日期：2012-10-01 00:00:00
abstract：:The primary objective of this phase 1, open-label, multicenter, 3-period, fixed-sequence study was to evaluate the effect of multiple doses of vemurafenib on the pharmacokinetics of a single dose of digoxin, a probe P-glycoprotein (P-gp) substrate, in patients with BRAFV600 mutation-positive metastatic malignancy. Fol...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1111
更新日期：2018-08-01 00:00:00
abstract：:The effects of graded doses of anisotropine methylbromide on nocturanl gastric secretion were investigated in a double-blind crossover study in man. Single doses considerably higher than those usually employed for daytime use in adjunctive therapy of peptic ulcer disease significantly reduced acid secretion without si...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1977.tb04583.x
更新日期：1977-01-01 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：:T Cell Modulatory Peptide (TCMP-80), L-lysine-L-serine, is a synthetic dipeptide structurally related to a selected amino acid sequence in human immunoglobulin G. Based on in vitro and preclinical in vivo testing, TCMP-80 has immunomodulatory properties. This report describes the first administration of TCMP-80 to man...
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.tb03605.x
更新日期：1990-04-01 00:00:00
abstract：:The half life (t1/2 ) of teneligliptin is 24.2 hours. Accordingly, we hypothesized that the administration of teneligliptin every other day might improve glycemic control. In this study, we evaluated the effectiveness of the administration of teneligliptin every other day in Japanese patients with type 2 diabetes. Fif...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.385
更新日期：2015-02-01 00:00:00
abstract：:A number of factors have been implicated in the interpatient variability of valproic acid (VPA) pharmacokinetics. These include patient age, concurrent anticonvulsant therapy, and dosage of VPA. In the clinical setting, it is important to determine which of these variables exert a major effect on the observed differen...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1985.tb02836.x
更新日期：1985-05-01 00:00:00
abstract：:To determine if ordinary doses of nitrates produce a significant increase in methemoglobin, methemoglobin levels were measured in 59 randomly selected patients with coronary artery disease and unstable angina pectoris who were receiving organic nitrate therapy. Patients were taking isosorbide dinitrate, 2% nitroglycer...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1984.tb01825.x
更新日期：1984-04-01 00:00:00
abstract：:This study evaluated the pharmacodynamics and pharmacokinetics of once-daily dosing of warfarin at steady state when taken concomitantly with once-daily doses of duloxetine. Healthy subjects with a stable international normalized ratio (INR) of 1.5 to 2.0 on an individualized fixed dose of warfarin (2-9 mg) in period ...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/0091270009344335
更新日期：2009-12-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1983.tb02715.x
更新日期：1983-04-01 00:00:00
abstract：:The integrated glucose-insulin (IGI) model is a previously published semimechanistic model that describes plasma glucose and insulin concentrations after glucose challenges. The aim of this work was to use knowledge of physiology to improve the IGI model's description of glucose absorption and gastric emptying after t...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.602
更新日期：2016-03-01 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
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1060
更新日期：2018-05-01 00:00:00
abstract：:Thirty-eight ambulatory patients with congestive cardiac failure took part in a double-blind clinical trial of 50 mg hydrochlorothiazide orally daily and slow-release formulation of 60 mg furosemide orally daily. Following a one-week period of placebo administration, patients were randomly allocated to the treatment w...
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.tb02644.x
更新日期：1982-11-01 00:00:00
abstract：:Twelve patients chronically maintained on warfarin were administered 80 mg atorvastatin for 2 weeks. Mean prothrombin times decreased slightly, but only for the first few days of the two-week treatment period. Thus atorvastatin had no consistent effect on the anticoagulant activity of warfarin and adjustment in warfar...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1997.tb04288.x
更新日期：1997-11-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.9
更新日期：2013-04-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.848
更新日期：2017-05-01 00:00:00
abstract：:Antibacterial drugs are among the most common medications used by pregnant women. While medical literature generally defines nitrofurantoin as an antibiotic that is safe for use during the first trimester of pregnancy, new concerns about a possible association between congenital malformations following exposure to nit...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.139
更新日期：2013-09-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1979.tb02474.x
更新日期：1979-02-01 00:00:00
abstract：:Compared with aminoglycosides, chloramphenicol, sulfonamides, tetracyclines, and even penicillins, the cephalosporins represent a remarkably safe class of antibiotics. Among the cephalosporins, the extended spectrum, third generation agents developed generally produce few side effects and appear to be less allergenic ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/j.1552-4604.1990.tb03476.x
更新日期：1990-05-01 00:00:00
abstract：:To explore the clinical relevance of inhibition of multidrug resistance transporter 1 and organic anion transporting polypeptide transporter, a drug-drug interaction study was conducted using aliskiren and cyclosporine. This was an open-label, single-sequence, parallel-group, single-dose study in healthy subjects. Sub...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270010385934
更新日期：2011-11-01 00:00:00
abstract：:Although there are many reports of the short-term effectiveness of antiarrhythmic drugs for suppression of ventricular ectopic depolarizations, there are less data available on the long-term use of these drugs. We treated 122 patients for up to 2 years with antiarrhythmic drugs for suppression of frequent ventricular ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1990.tb03466.x
更新日期：1990-03-01 00:00:00
abstract：:Many astronauts experience intolerance to orthostatic stress after space flight, despite the ingestion of salt tablets and water equivalent to 0.9% saline just before their return to Earth. Previous research indicates that the ingestion of 1.07% saline solution increased plasma volume more than did 0.9% saline. Theref...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1994.tb04978.x
更新日期：1994-05-01 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
doi：10.1002/jcph.1577
更新日期：2020-06-01 00:00:00
abstract：:The decrease in renal blood flow (RBF) observed in patients with hypertension can be increased with converting enzyme inhibition (CEI). It is unknown whether the decrease in RBF observed with age can also be increased with CEI. This study compared the short- and long-term effects of captopril monotherapy in young (les...
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
abstract：:Unresolved issues of ethical, methodological, and legal concerns in the use of normal healthy volunteers persist. Financial incentives in their recruitment offer a unique ethical dilemma because of questions surrounding payment. A review of literature was conducted to obtain research systematically examining volunteer...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：2002-04-01 00:00:00
