Abstract:
:A selective thromboxane A2 (TXA2) receptor blocking agent, vapiprost, was orally administered to healthy male Japanese volunteers to investigate the pharmacokinetic and pharmacodynamic properties. The time-profile of vapiprost concentration in plasma was determined and the effects of the drug on platelet aggregation in platelet-rich plasma (PRP) induced by a stable TXA2 receptor agonist U-46619, adenosine diphosphate (ADP) and collagen, and platelet aggregation in whole blood induced by U-46619 ex vivo were simultaneously examined and compared. In the single-dose study (5, 10, and 20 mg/man) the plasma concentrations of the drug were fitted well to a one-compartment open model with a first-order absorption. The area under plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) showed dose-related increases, whereas the mean elimination half-lives (t1/2) remained approximately constant within the range of 0.99-1.1 hour. The drug was hardly recovered unchanged in urine. The platelet aggregation in PRP induced by collagen or U-46619 and the secondary aggregation by ADP were inhibited; that induced by U-46619 was the most specifically and completely inhibited at 2 hours after administration of any dose. The duration for maintaining the significant inhibition tended to depend on the dose and ranged from 24 to 36 hours after administration, which was much longer than expected from the plasma concentration of drug. The time-profile of inhibiting whole blood platelet aggregation that was induced by U-46619 was almost parallel to that of platelet aggregation in PRP by the same aggregant. The bleeding time was slightly prolonged 2 and 8 hours after administrations of 10 and 20 mg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Uematsu T,Nagashima S,Mizuno A,Hirano K,Nakashima Mdoi
10.1002/j.1552-4604.1991.tb01917.xsubject
Has Abstractpub_date
1991-09-01 00:00:00pages
815-22issue
9eissn
0091-2700issn
1552-4604journal_volume
31pub_type
杂志文章abstract::The anxiolytic triazolobenzodiazepine alprazolam was administered to six male patients, aged 26 to 46 years, with panic disorder or agoraphobia (with panic attacks) to assess clinical effects and steady-state pharmacokinetics following multiple dosing at three levels: 3.0 mg/d, 6.0 mg/d, and 9.0 mg/d. Multiple-dose ki...
journal_title:Journal of clinical pharmacology
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doi:10.1002/j.1552-4604.1986.tb03526.x
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journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
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abstract::This report investigated safety and dosing recommendations of intravenous caspofungin in hepatic insufficiency. In the single-dose study, 8 patients each with mild and moderate hepatic insufficiency received 70 mg of caspofungin. In the multiple-dose study, 8 patients with mild hepatic insufficiency and 13 healthy mat...
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journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
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更新日期:1991-11-01 00:00:00
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journal_title:Journal of clinical pharmacology
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更新日期:1994-09-01 00:00:00
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journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,评审
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journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
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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
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