FIG 1.

Ivacaftor, M1, and M6 concentrations in murine plasma and ELF. (A) C57BL/6NCrlBR male mice (8 to 10 weeks of age) were infected with 1 × 10⁶ CFU of P. aeruginosa PAO1 by intratracheal administration. A non-infected control group was also tested in parallel. Thirty minutes after infection, the mice were treated with 3 mg/kg IVA in 10% PEG 400, 10% Tween 80, and 80% saline by intraperitoneal administration. Mice were sacrificed at 10 min and 1, 2, 6, and 24 h after IVA administration. Blood was collected and processed to obtain plasma. IVA, M1, and M6 concentrations in plasma were measured by HPLC-MS/MS. (B) BALF was collected and centrifuged, and the supernatant was used to quantify the IVA concentration. The volume of the ELF was determined by using the ratio of the urea concentration in BALF to that in plasma. The amounts of IVA and M1 were measured by HPLC-MS/MS. Data (derived from 3 to 4 mice) are represented as the mean values ± standard errors of the means (SEMs). Limits of quantification (LOQ) for IVA and its metabolites are indicated. A value corresponding to LOQ/2 was assigned to undetectable samples at specific time points (e.g., 10 min and/or 24 h). Statistical significance was calculated by the Mann-Whitney test comparing the infected and non-infected mouse groups at each time point.