Background Ivacaftor (Kalydeco) is the first drug to treat the molecular defect underlying cystic fibrosis (CF). To this end the substance appears to be effective only in patients with the G551D mutation in the CFTR gene. Due to the low number of patients currently treated, very little is known about the PK/PD relationship of ivacaftor.

Purpose Serum concentration measurements were used in order to control for adherence, to rule out dose-dependent side effects and to better understand the pharmacokinetics of ivacaftor.

Materials and methods Serum samples were obtained 3–4 h after intake of 150 mg ivacaftor by patients who had been treated with Kalydeco for at least 3 months. After deproteinisation, ivacaftor serum concentrations were determined using validated liquid chromatography with mass spectroscopic detection (LC-MS Q-TOF).

Results We were able to observe blood samples from 6 patients without impaired hepatic function and without co-administration of other CYP3 inhibitors. All were taking the standard dose of 2 × 150 mg/d. The ivacaftor levels appeared to vary from 400 to 3000 ng/ml. 5 of the 6 patients had significantly higher levels than those reported from the pivotal trials for ivacaftor.

Conclusions Our initial results demonstrated that ivacaftor serum levels in patients treated with the standard dosing scheme for ivacaftor (150 mg bid) were much higher than reported in the literature. Given the background information reported by the manufacturers in the SPC that an effective concentration 90% (EC90) is 405 ng/mL a dose reduction could be considered.

No conflict of interest.