Safety and Pharmacokinetics Following Oral or Intravenous Lefamulin in Adults With Cystic Fibrosis
Gregory S Sawicki1, Wolfgang W Wicha2, Tara S Hiley3
1Boston Children's Hospital, Boston, Massachusetts, USA.
Purpose:
Methicillin-resistant Staphylococcus aureus infections are increasing in prevalence in patients with cystic fibrosis (CF) and are associated with worsening lung function and increased mortality. Lefamulin is a pleuromutilin antimicrobial approved to treat community-acquired bacterial pneumonia based on potent in vitro activity and clinical efficacy. This Phase I, open-label, randomized crossover study assessed the safety and pharmacokinetic profile of oral and intravenous (IV) lefamulin in adults with CF.
Methods:
The study comprised 2 dosing periods in which adults with CF (N = 13) received a single dose of lefamulin via a 150-mg IV infusion or 600-mg immediate-release orally administered tablet, separated by a 4- to 7-day washout period. Pharmacokinetic and safety parameters were assessed after lefamulin treatment.
Findings:
Single doses of lefamulin administered via oral tablet or IV infusion resulted in comparable drug exposure, and sputum analysis suggested rapid penetration of lefamulin into the lung. Comparison of the present results with those obtained from prior single-dose studies of healthy volunteers indicate no meaningful difference in the pharmacokinetic properties of lefamulin in patients with CF. Treatment-emergent adverse events were consistent with previous reports, and the majority were mild in severity.
Implications:
These results show similar lefamulin pharmacokinetic and safety profiles between patients with CF and healthy volunteers receiving the same oral and IV doses, suggesting no need for lefamulin dose adjustment in patients with CF and indicating the potential of lefamulin as therapy for lung infections in patients with CF.
Clinicaltrials:
gov identifier: NCT05225805.
Insights
Lefamulin showed similar safety and drug exposure in cystic fibrosis patients compared to healthy volunteers. This suggests lefamulin may be a potential therapy for lung infections in CF patients without dose adjustment.
Area of Science:
- Pharmacology
- Infectious Diseases
- Pulmonology
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) infections are a growing concern in cystic fibrosis (CF) patients, leading to poorer lung function and higher mortality.
- Lefamulin, a pleuromutilin antimicrobial, is approved for community-acquired bacterial pneumonia due to its potent in vitro activity and clinical effectiveness.
Purpose of the Study:
- To evaluate the safety and pharmacokinetic profile of oral and intravenous (IV) lefamulin in adult patients with cystic fibrosis (CF).
- To compare lefamulin's pharmacokinetics and safety in CF patients with data from healthy volunteers.
Main Methods:
- A Phase I, open-label, randomized crossover study involving 13 adult CF patients.
- Participants received single doses of 150-mg IV lefamulin or a 600-mg oral tablet, with a 4- to 7-day washout period.
- Pharmacokinetic parameters and safety were assessed post-administration.
Main Results:
- Oral and IV lefamulin administration resulted in comparable drug exposure in CF patients.
- Sputum analysis indicated rapid penetration of lefamulin into the lungs.
- Adverse events were mild and consistent with previous lefamulin studies.
Conclusions:
- Lefamulin exhibits similar pharmacokinetic and safety profiles in CF patients and healthy volunteers.
- No dose adjustment for lefamulin appears necessary in CF patients.
- Lefamulin demonstrates potential as a therapeutic option for lung infections in individuals with cystic fibrosis.
More Related Videos
07:16Development of a Polymicrobial Colony Biofilm Model to Test Antimicrobials in Cystic Fibrosis
Published on: September 20, 2024
09:26Antibiotic Efficacy Testing in an Ex vivo Model of Pseudomonas aeruginosa and Staphylococcus aureus Biofilms in the Cystic Fibrosis Lung
Published on: January 22, 2021
Related Concept Videos
01:24Cystic Fibrosis: Management
Sinus disease and chronic...
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
01:11Renal Failure: Dose Adjustments
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
01:21Factors Affecting Drug Response: Overview
01:19Antiasthma Drugs: Leukotriene Modifiers
Leukotriene modifiers work through two distinct mechanisms:
01:23Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...