# 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.

## Key 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.