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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.
This article was published in the following journal.
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A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.
Ongoing scrutiny of a population (general population, study population, target population, etc.), generally using methods distinguished by their practicability, uniformity, and frequently their rapidity, rather than by complete accuracy.
The attitude of a significant portion of a population toward any given proposition, based upon a measurable amount of factual evidence, and involving some degree of reflection, analysis, and reasoning.
Differences in measurable biological values, characteristics, or traits, among individuals of a population or between population groups.
The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from PREVALENCE, which refers to all cases, new or old, in the population at a given time.
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