Pharmacokinetics and pharmacodynamics of oral grepafloxacin in patients with acute bacterial exacerbations of chronic bronchitis
| Autor: | David A. Collins, Jerome J. Schentag, Alan Forrest, Michael A. Amantea, Sanford Chodosh |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Microbiology (medical)
Adult Male medicine.medical_specialty Chronic bronchitis Time Factors Population Administration Oral Quinolones Models Biological Piperazines Pharmacokinetics Anti-Infective Agents Internal medicine medicine Humans Pharmacology (medical) education Bronchitis Antibacterial agent Aged Pharmacology Aged 80 and over education.field_of_study Analysis of Variance Bacteria Dose-Response Relationship Drug business.industry Bacterial Infections Middle Aged medicine.disease Grepafloxacin Surgery Infectious Diseases Pharmacodynamics Chronic Disease Sputum Female medicine.symptom business medicine.drug Fluoroquinolones |
| Zdroj: | The Journal of antimicrobial chemotherapy. 40 |
| ISSN: | 0305-7453 |
| Popis: | This analysis was designed to characterize the population pharmacokinetics and pharmacodynamics of oral grepafloxacin (OPC-17,116) in patients with acute bacterial exacerbations of chronic bronchitis (ABECB). The study group included 76 patients (43 male, 33 female) between 23 and 81 years of age, who were part of a multicentre, randomized, double-blind, dose-response study. Patients were randomly assigned to receive oral regimens of grepafloxacin, 200, 400 or 600 mg, each administered once daily for 14 days. Plasma samples for drug assay (typically eight per subject; four samples on either day 3, 4 or 5, plus troughs on other clinic visit days), were obtained during treatment. Population pharmacokinetic analysis was accomplished using iterative two-stage analysis. Cultures and quantitative Gram stains from serial 24 h collections of sputum were used to determine the time (in days) taken to eradicate each bacterial strain. Population pharmacodynamic analysis was performed for three measures of antibacterial response: probability of bacteriological cure, probability of clinical cure, and time to eradication. Grepafloxacin plasma concentration profiles were best fitted by a pharmacokinetic model with first-order absorption following a lag time between administration of the dose and onset of systemic absorption. All three measures of response were strongly related to the 24 h AUIC (AUC/MIC). At an AUIC of75, the percent probability of clinical cure was 71%; at an AUIC of 75-175, it was 80% (P0.05) and at an AUIC of175, it was 98% (P0.01). In conclusion, antibacterial response for grepafloxacin in ABECB patients was highly related to AUIC; values of75 appear inadequate and values of175 were optimal. |
| Databáze: | OpenAIRE |
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