title: Sputum and serum pharmacokinetics of loracarbef (LY163892) in patients with chronic bronchial sepsis.
abstract: Sputum and serum pharmacokinetics of loracarbef (LY163892) were performed in 19 patients with purulent bronchiectasis. Nine of the patients received 200 mg twice daily and ten patients, 400 mg twice daily, for a total of 14 days. beta-Lactamase activity was measurable in the lung secretions of all 19 patients at the start of therapy. Mean peak serum concentrations of 11.7 mg/L (S.E.M. 1.7) were recorded at 1 h after administration of 200 mg doses on day 2 of therapy and were 18.5 mg/L (S.E.M. 1.9) at 1.5 h in the 400 mg group. Loracarbef was shown to penetrate lung secretions even in the presence of beta-lactamase activity. Mean peak sputum concentrations were achieved between 2 and 4 h following dosing and were 0.2 mg/L (S.E.M. 0.05) in the 200 mg group and 0.4 mg/L (S.E.M. 0.08) in the 400 mg group. On days 7 and 14 of therapy, sputum loracarbef concentrations were similar 4 h after the morning dose (0.23 mg/L following 200 mg; 0.35 mg/L after 400 mg). These concentrations were approximately 2% of the peak serum concentration and penetration into lung secretions is similar to other beta-lactams.
authors.affiliation: Lung Immunobiochemical Research Laboratory, General Hospital, Birmingham, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Hill
authors.forename: D
authors.initials: D
authors.lastname: Bilton
authors.forename: M M
authors.initials: MM
authors.lastname: Johnson
authors.forename: A
authors.initials: A
authors.lastname: Pye
authors.forename: J L
authors.initials: JL
authors.lastname: Mitchell
authors.forename: R A
authors.initials: RA
authors.lastname: Stockley
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001987:Bronchiectasis / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D002511:Cephalosporins / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000378:metabolism; D013183:Sputum / Q000201:enzymology / Q000378:metabolism* / Q000382:microbiology; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000418:Albumins; D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D012709:Serum Albumin; C054920:loracarbef; D001618:beta-Lactamases