Ivacaftor pharmacokinetics and lymphatic transport after enteral administration in rats

TL;DR

This study examines how ivacaftor, a drug for cystic fibrosis, is absorbed and transported in rats, focusing on its lymphatic transport and food effect.

Contribution

The study quantifies the role of lymphatic transport in ivacaftor absorption and challenges its connection to the drug's food effect.

Findings

Ivacaftor oral bioavailability was 18.4% and 16.2% for aqueous suspension and oil solution, respectively.

Lymphatic transport contributed 5.91% and 4.35% to overall bioavailability for the two formulations.

Lymphatic transport plays a minor role in ivacaftor absorption, suggesting other factors drive its food effect.

Abstract

Background: Ivacaftor is a modern drug used in the treatment of cystic fibrosis. It is highly lipophilic and exhibits a strong positive food effect. These characteristics can be potentially connected to a pronounced lymphatic transport after oral administration.

Methods: A series of studies was conducted to describe the basic pharmacokinetic parameters of ivacaftor in jugular vein cannulated rats when dosed in two distinct formulations: an aqueous suspension and an oil solution. Additionally, an anesthetized mesenteric lymph duct cannulated rat model was studied to precisely assess the extent of lymphatic transport.

Results: Mean ± SD ivacaftor oral bioavailability was 18.4 ± 3.2% and 16.2 ± 7.8%, respectively, when administered as an aqueous suspension and an oil solution. The relative contribution of the lymphatic transport to the overall bioavailability was 5.91 ± 1.61% and 4.35 ± 1.84%, respectively.

Conclusion: Lymphatic transport plays only a minor role in the process of ivacaftor intestinal absorption, and other factors are, therefore, responsible for its pronounced positive food effect.

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