Intestinal delivery in a long-chain fatty acid formulation enables lymphatic transport and systemic exposure of orlistat.
Int J Pharm
; 596: 120247, 2021 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-33486039
ABSTRACT
Orlistat is a pancreatic lipase (PL) inhibitor that inhibits dietary lipid absorption and is used to treat obesity. The oral bioavailability of orlistat is considered zero after administration in standard formulations. This is advantageous in the treatment of obesity. However, if orlistat absorption could be improved it has the potential to treat diseases such as acute and critical illnesses where PL transport to the systemic circulation via gut lymph promotes organ failure. Orlistat is highly lipophilic and may associate with intestinal lipid absorption pathways into lymph. Here we investigate the potential to improve orlistat lymph and systemic uptake through intestinal administration in lipid formulations (LFs). The effect of lipid type, lipid dose, orlistat dose, and infusion time on lymph and systemic availability of orlistat was investigated. After administration in all LFs, orlistat concentrations in lymph were greater than in plasma, suggesting direct transport via lymph. Lymph and plasma orlistat derivative concentrations were ~8-fold greater after administration in a long-chain fatty acid (LC-FA) compared to a lipid-free, LC triglyceride (LC-TG) or medium-chain FA (MC-FA) formulation. Overall, administration of orlistat in a LC-FA formulation promotes lymph and systemic uptake which may enable treatment of diseases associated with elevated systemic PL activity.
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01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Graxos
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Linfa
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article