| Disposition of acrivastine in the male beagle dog. | |
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MedLine Citation:
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PMID: 1358572 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Three male beagle dogs were given 10 mg/kg iv and oral doses of [14C]acrivastine, a novel nonsedating antihistaminic agent, in a nonrandomized crossover experiment. Urine and feces were collected for 72 hr after dosing. After iv dosing, a mean of 34% was recovered in the urine, and 63% was recovered in the feces. After po dosing, a mean of 29% of the radiocarbon was recovered in the urine, and 63% was recovered in the feces (dose adjusted for 14% lost in vomitus). Acrivastine and three major metabolites were detected in the excreta. The metabolites were identified as a side-chain-reduced analog of acrivastine (metabolite 3, 270C81), a gamma-aminobutyric acid analog of 270C81 (metabolite 2), and a benzoic acid analog of 270C81 (metabolite 1). After iv dosing, 34% of the dose was excreted as parent drug, 21% as metabolite 3, 15% as metabolite 2, and 6% as metabolite 1, while after po dosing, 35% of the dose was excreted as parent drug, 18% as metabolite 3, 11% as metabolite 2, and 7% as metabolite 1. Pharmacokinetic analysis of acrivastine plasma concentration-time curves after both routes of administration indicated a mean total body clearance of 17.3 ml/min/kg, a Vss of 0.93 liter/kg, a terminal half-life of 0.7 hr, and an oral bioavailability of 40%. The apparent plasma half-life of the metabolite, 270C81, was 1.5 hr. Analysis of AUC values indicated that greater amounts of 270C81 than acrivastine circulated in plasma after both iv and po dosing, and that first-pass metabolism of acrivastine to 270C81 occurred. The results indicated that acrivastine was extensively metabolized in the dog to 270C81 and suggested that 270C81 itself underwent further metabolism to metabolites 1 and 2. |
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Authors:
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M J McNulty; D L Deal; F R Nelson; S Weller; P Chandrasurin; J Shockcor; J W Findlay |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Drug metabolism and disposition: the biological fate of chemicals Volume: 20 ISSN: 0090-9556 ISO Abbreviation: Drug Metab. Dispos. Publication Date: 1992 Sep-Oct |
Date Detail:
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Created Date: 1992-12-23 Completed Date: 1992-12-23 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9421550 Medline TA: Drug Metab Dispos Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 679-87 Citation Subset: IM |
Affiliation:
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Wellcome Research Laboratories, Burroughs Wellcome Co., Research Triangle Park, NC 27709. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chromatography, High Pressure Liquid Dogs Histamine H1 Antagonists / pharmacokinetics* Male Triprolidine / analogs & derivatives*, pharmacokinetics |
| Chemical | |
Reg. No./Substance:
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0/Histamine H1 Antagonists; 486-12-4/Triprolidine; 87848-99-5/acrivastine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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