| The effects of age and gender on the pharmacokinetics and pharmacodynamics in healthy subjects of the plasminogen activator, lanoteplase. | |
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MedLine Citation:
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PMID: 21545481 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: To investigate the influence of age and gender on the intravenous pharmacokinetics and pharmacodynamics of the plasminogen activator, lanoteplase. METHODS: Forty healthy subjects (10 each of young males, elderly males, young females and elderly females) received a single bolus 10 kU kg(-1) intravenous dose of lanoteplase. Plasma from blood serially collected for 24 h post-dose was analyzed for lanoteplase (antigen), fibrinogen, plasminogen and α2-antiplasmin concentrations, plasma plasminogen activation activity (PPAA) and rapid plasminogen activator inhibitor (PAI-1). RESULTS: Lanoteplase mean total systemic clearance (CL(t)) values ranged from 1.9 to 2.8 l h(-1) and mean steady-state volume of distribution (V(ss)) values ranged from 12.3 to 15.6 l. Age-by-gender interactions were observed for lanoteplase CL(t) (P= 0.04), but no differences were observed for V(ss) or elimination half-life. Elderly females had a 27% lower mean CL(t) than young females (95% CI for the difference 0.17, 1.27 l h(-1)) and 32% lower CL(t) than elderly males (95% CI for the difference 0.15, 1.65 l h(-1)). PPAA AUC/dose values did not show an age-by-gender interaction. Haemostasis parameters indicated only a slight degree of systemic plasminogen activation. CONCLUSIONS: Elderly females had a lower mean lanoteplase CL(t) than elderly males and young females. However, no difference was observed between young and elderly females for the AUC/dose of PPAA. In addition, there were no age-related or gender-related differences observed in the other pharmacodynamic parameters measured. |
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Authors:
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Nimish N Vachharajani; Ralph H Raymond; Wen-Chyi Shyu; Bruce C Stouffer; David W Boulton |
Publication Detail:
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Type: Clinical Trial; Journal Article |
Journal Detail:
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Title: British journal of clinical pharmacology Volume: 72 ISSN: 1365-2125 ISO Abbreviation: Br J Clin Pharmacol Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-10-12 Completed Date: 2012-02-09 Revised Date: 2013-05-24 |
Medline Journal Info:
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Nlm Unique ID: 7503323 Medline TA: Br J Clin Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 775-86 Citation Subset: IM |
Copyright Information:
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© 2011 Bristol-Myers Squibb, Co. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society. |
Affiliation:
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Bristol-Myers Squibb Research and Development, Princeton, New Jersey 08543-4000, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Age Factors Aged Analysis of Variance Area Under Curve Blood Coagulation / drug effects* Dose-Response Relationship, Drug Female Humans Male Middle Aged Plasminogen Activators / pharmacokinetics*, pharmacology Sex Factors Tissue Plasminogen Activator / pharmacokinetics*, pharmacology Young Adult |
| Chemical | |
Reg. No./Substance:
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153484-31-2/SUN 9216; EC 3.4.21.-/Plasminogen Activators; EC 3.4.21.68/Tissue Plasminogen Activator |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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