Document Detail


The development of a sensitive and specific enzyme immunoassay for FK480, a novel cholecystokinin type-A receptor antagonist, in human plasma.
MedLine Citation:
PMID:  9800657     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A sensitive and specific enzyme immunoassay for FK480, a novel cholecystokinin type-A (CCK-A) receptor antagonist, was developed to study the pharmacokinetics of the drug at low-dose administration using a specific monoclonal antibody. The high performance liquid chromatography (HPLC) method had been used for studying toxicokinetics, but its determination limit (2.5 ng ml-1) was too high for use in clinical studies. Subsequently we developed an enzyme immunoassay (EIA) using rabbit anti-FK480 serum (polyclonal antibody). It had higher sensitivity (0.1 ng ml-1) when 0.5 ml of plasma was used but its specificity was low because of the cross-reactivity of the metabolites of FK480. Therefore we produced several monoclonal antibodies for FK480 by cell fusion, and selected the antibody which was least cross-reactive for the isolated metabolites of FK480. Finally we developed a sensitive and specific EIA using this monoclonal antibody. The lower limit of quantification of this method was 0.2 ng ml-1 when 0.2 ml of human plasma was used. The coefficient of variation over the calibration range (0.2-10 ng ml-1) was less than 15%. We used this method for clinical studies, and it showed a good correlation to the HPLC method when plasma concentration was 2.5 ng ml-1 or more.
Authors:
K Nozaki; S Suzuki; F Maeda; S Takagaki; A Suzuki; T Hata
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of pharmaceutical and biomedical analysis     Volume:  17     ISSN:  0731-7085     ISO Abbreviation:  J Pharm Biomed Anal     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1999-01-13     Completed Date:  1999-01-13     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8309336     Medline TA:  J Pharm Biomed Anal     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1381-92     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal
Benzodiazepinones / blood*,  immunology,  metabolism,  pharmacokinetics
Chromatography, High Pressure Liquid
Cross Reactions
Dogs
Female
Hormone Antagonists / blood*,  immunology,  metabolism,  pharmacokinetics
Humans
Immunoenzyme Techniques
Indoles / blood*,  immunology,  metabolism,  pharmacokinetics
Male
Mice
Mice, Inbred BALB C
Rabbits
Rats
Rats, Sprague-Dawley
Receptors, Cholecystokinin / antagonists & inhibitors*
Sensitivity and Specificity
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Benzodiazepinones; 0/Hormone Antagonists; 0/Indoles; 0/Receptors, Cholecystokinin; 150408-73-4/FR 120480

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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