title: Pharmacokinetic/pharmacodynamic predictors of time to clinical resolution in patients with acute bacterial exacerbations of chronic bronchitis treated with a fluoroquinolone.
abstract: Forty nine subjects with acute bacterial exacerbations of chronic bronchitis (ABECB) treated with grepafloxacin were evaluated for parameters predictive of clinical outcome. Signs and symptoms associated with ABECB were serially collected and evaluated for changes. Coughs per day, sputum volume and the percentage of sputum neutrophils were associated with clinical outcome. A by groups analysis, based on clinical success was performed using Cox regression analysis to determine factors associated with time to clinical success and time to reduction in sputum volume, coughs per day and sputum neutrophil percent. Factors evaluated included AUIC (AUC/MIC), isolate species, years and type of underlying lung disease, alcohol use, smoking history and number of ABECB within the previous 12 months. AUIC<276 (mg h/l)/mg/l (P<0.03) and or the presence of mild bronchiectasis (P<0.01) were associated with longer time to clinical success. In addition a relationship was found between AUIC>212 (mg h/l)/mg/l (P<0.01) and AUIC>576 (mg h/l)/mg/l (P<0.02) and decreasing days to sputum volume reduction and coughs per day, respectively. A diagnosis of mild bronchiectasis prolonged the time to reduce coughs per day (P<0.03) and neutrophil percentage (P<0.01). Patients with mild bronchiectasis were found to have an increase in the time to clinical success, coughs per day improvement and sputum neutrophil percent improvement. AUIC is an important PK/PD parameter predictive of successful outcome in ABECB, even in subjects with mild bronchiectasis. Grepafloxicin has been withdrawn from sale since these studies were carried out. This work is published to illustrate the relationship between pharmacodynamics and clinical efficacy and the use of AUIC as a valuable predictive parameter for fluoroquinolones.
authors.affiliation: SUNY at Buffalo School of Pharmacy and The Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Kaleida Health, 3 Gates Circle, Buffalo, NY 14209, USA.
authors.forename: B
authors.initials: B
authors.lastname: Meinl
authors.forename: J M
authors.initials: JM
authors.lastname: Hyatt
authors.forename: A
authors.initials: A
authors.lastname: Forrest
authors.forename: S
authors.initials: S
authors.lastname: Chodosh
authors.forename: J J
authors.initials: JJ
authors.lastname: Schentag
mesh_terms: D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001991:Bronchitis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology / Q000401:mortality; D002908:Chronic Disease; D018849:Controlled Clinical Trials as Topic; D005260:Female; D024841:Fluoroquinolones; D006193:Haemophilus influenzae / Q000187:drug effects; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D001936:Moraxella catarrhalis / Q000187:drug effects; D010879:Piperazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D010879:Piperazines; C075375:grepafloxacin