Pharmacokinetics (PK) and absolute bioavailability (F) of linezolid (L) in cystic fibrosis (CF) patients (PTS)

Abstract

Introduction Methicillin- & vancomycin-resistant bacteria are increasingly responsible for CF exacerbations. L is highly active against these pathogens. We studied L first dose (FD) & steady-state (SS) PK in CF Pts. Methods CF pts received L-IV and then orally when indicated as part of their hospitalized clinical care. 12 blood samples & 4 timed urine aliquots were obtained over 24hrs after FD (2nd IV dose held) & 9 blood samples again at SS (dosed q8–12h). Quantitation of L and 2 inactive metabolites were determined by HPLC; standard non-compartment PK methodology was used. Results 10 pts (5 males) studied thus far; data analyzed for 7. Plasma L concentration-time curves reflect 2-compartment character. Mean(±)SD L PK after FD:t½-4.6 (1.9) hrs;Vd-0.67 (0.09) L/Kg; Cl-2.6 (1) ml/min/Kg. No differences were observed between FD & SS PK. ~18% of IV dose excreted in urine over 24hrs. Median L oral F was 110% of IV dose administered. L metabolites M25 & M23 accounted for ~24% & 5% of parent L plasma concentrations, respectively. These L PK data in CF are consistent with L PK data obtained in 39 non-CF Pts of similar age. Conclusions Our preliminary L CF PK data support conventional age-appropriate L dosing & employing a 1 to 1 conversion for IV to oral switch in the treatment of CF patients. Clinical Pharmacology & Therapeutics (2005) 77, P30–P30; doi: 10.1016/j.clpt.2004.12.006