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 elimination half-life was unusually long (>200 hours). The unbound fraction in human plasma was also much smaller than that in dogs, rats and mice, as was the binding of UCN-01 to human alpha-1 acid glycoprotein much stronger than that to human serum albumin or human gamma-globulin. The association constants for alpha-1 acid glycoprotein and human plasma were approximately 8 x 10(8)(mol/L)(-1), indicating extremely high affinity. In this review article, the authors discuss the pharmacologic features of UCN-01 across species and provide a perspective on how this information could be applied prospectively to the future development of this agent.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Fuse E,Kuwabara T,Sparreboom A,Sausville EA,Figg WDdoi
10.1177/0091270005274549subject
Has Abstractpub_date
2005-04-01 00:00:00pages
394-403issue
4eissn
0091-2700issn
1552-4604pii
45/4/394journal_volume
45pub_type
杂志文章,评审abstract::The pharmacokinetics and pharmacodynamics of ranitidine were studied in 13 term neonates with stable renal and hepatic function who were treated with extracorporeal membrane oxygenation (ECMO). Ranitidine was initially administered as a single 2 mg/kg dose over 10 minutes and intragastric pH was monitored to determine...
journal_title:Journal of clinical pharmacology
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abstract::Faldaprevir is a potent hepatitis C virus (HCV) NS3/4A protease inhibitor and an inhibitor of UDP-glucuronosyltransferase-1A1 (UGT1A1), which is involved in raltegravir clearance. Raltegravir, an HIV integrase inhibitor, may be used in combination with HCV treatment in HCV/HIV co-infected patients. In this open-label,...
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journal_title:Journal of clinical pharmacology
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更新日期:1998-08-01 00:00:00
abstract::To compare the steady-state kinetic profiles and ectopy-suppression rates of two sustained-release forms of quinidine with those of a conventional quinidine preparation, 18 patients with ventricular ectopy were studied in randomized crossover fashion. The drugs were conventional quinidine sulfate 300 mg q6h, sustained...
journal_title:Journal of clinical pharmacology
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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 rec...
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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
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journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
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abstract::Troglitazone, a PPAR-gamma agonist, enhances the actions of insulin on muscle and liver. It is metabolized predominantly in the liver to a sulfate conjugate and a quinone metabolite. Acetaminophen also undergoes metabolism by conjugation. This three-way crossover study in 12 healthy male volunteers was conducted to in...
journal_title:Journal of clinical pharmacology
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abstract::The extension of the previously developed integrated models for glucose and insulin (IGI) to include the oral glucose tolerance test (OGTT) in healthy volunteers could be valuable to better understand the differences between healthy individuals and those with type 2 diabetes mellitus (T2DM). Data from an OGTT in 23 he...
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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
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abstract::The effect of pomegranate juice (PJ) or grapefruit juice (GFJ) on CYP3A activity was studied in vitro and in healthy human volunteers. In human liver microsomes, the mean 50% inhibitory concentrations (IC(50)) for PJ and GFJ versus CYP3A (triazolam alpha-hydroxylation) were 0.61% and 0.55%, (v/v) respectively, without...
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
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journal_title:Journal of clinical pharmacology
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journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
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abstract::Glucagon is a counter-regulatory hormone that is classically used to treat hypoglycemia. However, it can elicit the generation of cAMP within the myocardium to cause positive inotropic and chronotropic effects without the need for beta-1 adrenoceptor stimulation. Glucagon has been used extensively to treat beta-blocke...
journal_title:Journal of clinical pharmacology
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更新日期:1999-05-01 00:00:00
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abstract::The type II histamine receptor antagonists, cimetidine and ranitidine, widely used in treatment of peptic ulcer disease have been reported to cause bradycardia. To evaluate the cardiovascular effects of H2 antagonists nineteen healthy volunteers were entered into a double-blind crossover comparison of cimetidine 300 m...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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更新日期:1989-05-01 00:00:00
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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
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abstract::Pain is considered the most common complaint worldwide for which patients seek treatment. Conventional analgesic agents play an important role in modern pain therapy, but they cause several adverse effects. Therefore, newer and better analgesics continue to be investigated. In this controlled clinical trial, the autho...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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journal_title:Journal of clinical pharmacology
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abstract::The selective T-cell costimulation modulator abatacept is approved for treatment of adult rheumatoid arthritis (RA) and polyarticular juvenile idiopathic arthritis (pJIA; 6-17 years [intravenous] and 2-17 years [subcutaneous]). An extrapolation approach was taken to determine subcutaneous weight-tiered doses of abatac...
journal_title:Journal of clinical pharmacology
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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
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