Role of P-glycoprotein and cytochrome P450 3A in limiting oral absorption of peptides and peptidomimetics.
J Pharm Sci
; 87(11): 1322-30, 1998 Nov.
Article
em En
| MEDLINE
| ID: mdl-9811484
ABSTRACT
Cytochrome P450 3A4 (CYP3A4), the major phase I drug metabolizing enzyme in humans, and the MDR1 gene product P-glycoprotein (P-gp) are present at high concentrations in villus tip enterocytes of the small intestine and share a significant overlap in substrate specificity. A large body of research both in vitro and in vivo has established metabolism by intestinal CYP3A4 as a major determinant of the systemic bioavailability of orally administered drugs. More recently it has been recognized that drug extrusion by intestinal P-gp can both reduce drug absorption and modulate the effects of inhibitors and inducers of CYP3A-mediated metabolism. There is relatively little data regarding the effects of CYP3A and P-gp on peptide drugs; however, studies with the cyclic peptide immunosuppresant cyclosporine as well as peptidomimetics such as the HIV-protease inhibitor saquinavir (Invirase) and a new cysteine protease inhibitor K02 (Morpholine-Urea-Phe-Hphe-Vinyl sulfone; Axys Pharmaceuticals) provide some insight into the impact of these systems on the oral absorption of peptides.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxirredutases N-Desmetilantes
/
Peptídeos
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Hidrocarboneto de Aril Hidroxilases
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Sistema Enzimático do Citocromo P-450
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Intestino Delgado
Limite:
Humans
Idioma:
En
Revista:
J Pharm Sci
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA