First population pharmacokinetic analysis showing increased quinolone metabolite formation and clearance in cystic fibrosis patients compared to healthy volunteers.

08:00 EDT 1st August 2018 | BioPortfolio

Summary of "First population pharmacokinetic analysis showing increased quinolone metabolite formation and clearance in cystic fibrosis patients compared to healthy volunteers."

Understanding the pharmacokinetics in cystic fibrosis (CF) patients is important for dosing. For antibiotics with extensive metabolism, however, a comparison of metabolite formation and elimination between CF-patients and healthy volunteers has never been performed via population modeling. We aimed to compare the population pharmacokinetics of fleroxacin and its N‑oxide and demethyl metabolites between CF-patients and healthy volunteers. Our analysis included eleven adult CF-patients and twelve healthy volunteers who received 800 mg fleroxacin as a single oral dose followed by five doses every 24 h from a previously published study. All plasma concentrations and amounts in urine for fleroxacin and its metabolites were simultaneously modelled. The estimates below accounted for differences in body size and body composition via allometric scaling by lean body mass. Oral absorption was slower in CF-patients than in healthy volunteers. For fleroxacin, the population mean in CF-patients divided by that in healthy volunteers was 1.12 for renal clearance, 1.01 for linear nonrenal clearance, 0.83 for saturable exsorption clearance into intestine, and 0.81 for volume of distribution. The formation clearances of N‑oxide fleroxacin and N‑demethylfleroxacin were 0.520 L/h and 0.496 L/h in CF-patients; these formation clearances were 0.378 L/h and 0.353 L/h in healthy volunteers. Renal clearance in CF-patients divided by that in healthy volunteers was 1.53 for N‑oxide fleroxacin and 1.70 for N‑demethyl fleroxacin. Allometric scaling by lean body mass best explained the variability. While fleroxacin pharmacokinetics was comparable, both formation and elimination clearances of its two metabolites were substantially larger in CF-patients compared to those in healthy volunteers.


Journal Details

This article was published in the following journal.

Name: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
ISSN: 1879-0720


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