The class
Two CETP inhibitors reach systemic circulation mainly via lymphatic transport, 22 to 28% of dose (Pharm Res 2010)
Original title: The mechanism of lymphatic access of two cholesteryl ester transfer protein inhibitors (CP524,515 and CP532,623) and evaluation of their impact on lymph lipoprotein profiles
Investigating how CETP inhibitors CP524,515 and CP532,623 reach systemic circulation, researchers found both compounds were highly lymphatically transported, accounting for 22 to 28% of the administered dose. Lymphatic transport correlated closely with each drug's affinity for lymph lipoproteins rather than solubility in lipoprotein core or surface lipids. Both inhibitors altered the kinetics of lymph lipid transport and reduced lipid transport within chylomicrons, indicating that CETP inhibitor therapy can reshape intestinal lipoprotein processing at the point of absorption, a mechanism that may contribute to the systemic lipoprotein changes observed during treatment.
Original abstract
Purpose: To explore the mechanism of lymphatic access of the CETP inhibitors (CETPi) CP524,515 and CP532,623 and probe their potential effect on lymph lipoprotein development.
Methods: Lymphatic access mechanisms were examined via correlation of lymphatic drug transport profiles with drug affinity for lymph lipoproteins and drug solubility in representative combinations of lipoprotein lipids. The effects of the CETPi on lymph lipoprotein profiles were evaluated by ultracentrifugation and flow cytometry.
Results: Both CETPi were highly lymphatically transported (22-28% of dose), and lymphatic transport was closely correlated with drug affinity for ex-vivo lymph lipoproteins or triglyceride emulsions and poorly related to solubility in mixtures of lipoprotein core and/or surface lipids. Both CETPi altered the kinetics of lymph lipid transport and decreased lymph lipid transport in chylomicrons.
Conclusion: Lymphatic transport of the CETPi appears to reflect high affinity for the interface of lymph lipoproteins rather than solubilisation in the lipoprotein core and confirms that triglyceride solubilities >50 mg/g are not necessarily a pre-requisite for lymphatic transport. The CETPi also led to changes to lipoprotein processing in the enterocyte including a reduction in lipid transport in chylomicrons. Changes to intestinal lipoprotein profiles may contribute to the changes in systemic lipoprotein levels seen during CETPi therapy.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.