Lack of an Effect of Polysorbate 80 on Intestinal Drug Permeability in Humans.
Pharm Res
; 39(8): 1881-1890, 2022 Aug.
Article
em En
| MEDLINE
| ID: mdl-35672541
ABSTRACT
PURPOSE:
Despite no broad, direct evidence in humans, there is a potential concern that surfactants alter active or passive drug intestinal permeation to modulate oral drug absorption. The purpose of this study was to investigate the impact of the surfactant polysorbate 80 on active and passive intestinal drug absorption in humans.METHODS:
The human (n = 12) pharmacokinetics (PK) of three probe substrates of intestinal absorption, valacyclovir, chenodeoxycholic acid (CDCA), and enalaprilat, were assessed. Endogenous bile acid levels were assessed as a secondary measure of transporter and microbiota impact.RESULTS:
Polysorbate 80 did not inhibit peptide transporter 1 (PepT1)- or apical sodium bile acid transporter (ASBT)-mediated PK of valacyclovir and CDCA, respectively. Polysorbate 80 did not increase enalaprilat absorption. Modest increases in unconjugated secondary bile acid Cmax ratios suggest a potential alteration of the in vivo intestinal microbiota by polysorbate 80.CONCLUSIONS:
Polysorbate 80 did not alter intestinal membrane fluidity or cause intestinal membrane disruption. This finding supports regulatory relief of excipient restrictions for Biopharmaceutics Classification System-based biowaivers.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polissorbatos
/
Enalaprilato
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos