ArticleFrontiers in pharmacology2026
Oral losartan yields subtherapeutic airway exposure compared to nebulized delivery and fails to improve mucociliary clearance in cystic fibrosis.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03435939 (Anti-Inflammatory Therapy to Augment CFTR Rescue in CF Patients), which is not on this map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Anti-Inflammatory Therapy to Augment CFTR Rescue in CF Patients
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10 authors.
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Abstract
Background: Transforming growth factor-β1 (TGF-β1) contributes to more severe pulmonary disease in people with cystic fibrosis (pwCF). Our preclinical Methods: We conducted comparative pharmacokinetics studies in sheep assessing airway surface liquid (ASL) concentrations of losartan and its metabolites, EXP3179 and EXP3174, after oral and inhaled administration. Another pharmacokinetic study used oral losartan to compare serum levels in pwCF on and off CFTR modulators and healthy volunteers. Finally, an open-label clinical trial evaluated effects of oral losartan (50 mg twice daily for 14 weeks) on mucociliary and cough clearance (MCC/CC) in pwCF off CFTR modulators as they have a need for novel therapies (NCT03435939). Results: In sheep, oral losartan (50 mg twice daily for 4 days) did not achieve ASL levels expected to improve CF-associated mucociliary dysfunction based on our previous data. In humans, single dose pharmacokinetics of oral losartan showed differential results in pwCF and healthy volunteers, with pwCF off CFTR modulators achieving the lowest serum levels of losartan and EXP3174 with a complete absence of EXP3179, the anti-inflammatory metabolite of losartan. The open label study included seven participants. Serum concentrations of losartan and EXP3174 at week 14 matched levels observed in pwCF not on modulators in the pharmacokinetic study. As expected, no improvements in whole-lung or peripheral MCC/CC were found in participants with complete datasets. PpFEV1 remained unchanged, but nasal TGF-β1 levels significantly decreased with treatment, although systemic inflammatory markers were unaffected (C-reactive protein, calprotectin, and serum amyloid A). Conclusion: Reduced drug exposure compared to healthy volunteers reflects altered pharmacokinetics in pwCF. Nevertheless, oral losartan at clinically approved doses does not achieve airway concentrations needed to restore mucociliary function in any individual, and especially not in pwCF off modulators. Future studies should consider inhaled drug delivery to achieve therapeutically meaningful airway exposure to losartan and its metabolites.
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