The Pharmacokinetic Changes in Cystic Fibrosis Patients Population: Narrative Review

Abstract

Cystic fibrosis (CF) is a rare genetic disorder commonly affecting multiple organs such as the lungs, pancreas, liver, kidney, and intestine. Our search focuses on the pathophysiological changes that affect the drugs' absorption, distribution, metabolism, and excretion (ADME). This review aims to identify the ADME data that compares the pharmacokinetics (PK) of different drugs in CF and healthy subjects. The published data highlight multiple factors that affect absorption, such as the bile salt precipitation and the gastrointestinal pH. Changes in CF patients' protein binding and body composition affected the drug distribution. The paper also discusses the factors affecting metabolism and renal elimination, such as drug-protein binding and metabolizing enzyme capacity. The majority of CF patients are on multidrug therapy, which increases the risk of drug-drug interactions (DDI). This is particularly true for those receiving the newly developed transmembrane conductance regulator (CFTR), as they are at a higher risk for CYP-related DDI. Our research highlights the importance of meticulously evaluating PK variations and DDIs in drug development and the therapeutic management of CF patients.

Keywords: absorption; cystic fibrosis; drug–drug interaction; gastrointestinal tract; pH; pharmacokinetics; protein binding; residence time; special population; transmembrane conductance regulator (CFTR); volume of distribution.

Figure 1

Literature search with excluded and included study numbers of PK in CF.

Figure 2

(A) Effects of CYP3A4/5 enzyme substrates and inhibitors on ivacaftor, a CYP3A4/5 enzyme metabolizer. (B) Effects of CYP3A4/5 enzyme inducers on ivacaftor, a CYP3A4/5 enzyme metabolizer.