Pharmacokinetics and biologic activity of the novel mast cell inhibitor, 4-(3-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline in mice.
Pharm Res
; 16(1): 117-22, 1999 Jan.
Article
em En
| MEDLINE
| ID: mdl-9950289
ABSTRACT
PURPOSE:
The purpose of the present study was to examine the pharmacodynamic and pharmacokinetic features of the novel mast cell inhibitor 4-(3'-Hydroxyphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P180) in mice.METHODS:
A high performance liquid chromatography (HPLC)-based quantitative detection method was used to measure plasma WHI-P180 levels in mice. The plasma concentration-time data was fit to a single compartment pharmacokinetic model by using the WinNonlin program to calculate the pharmacokinetic parameters. A cutaneous anaphylaxis model was used to examine the pharmacodynamic effects of WHI-P180 on anaphylaxis-associated vascular hyperpermeability.RESULTS:
The elimination half-life of WHI-P180 in CD-1 mice (BALB/ c mice) following i.v., i.p., or p.o. administration was less than 10 min. Systemic clearance of WHI-P180 was 6742 mL/h/kg in CD-I mice and 8188 mL/h/kg in BALB/c mice. Notably, WHI-P180, when administered in two consecutive nontoxic i.p. bolus doses of 25 mg/kg, inhibited IgE/antigen-induced vascular hyperpermeability in a well-characterized murine model of passive cutaneous anaphylaxis.CONCLUSIONS:
WHI-P180 is an active inhibitor of IgE-mediated mast cell responses in vitro and in vivo. Further preclinical characterization of WHI-P180 may improve the efficacy of WHI-P180 in vivo and provide the basis for design of effective treatment and prevention programs for mast cell mediated allergic reactions.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
/
Imunoglobulina E
/
Mastócitos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos