title: [Evaluation of target attainment rate of pazufloxacin mesilate using Monte Carlo simulation method].
abstract: We calculated achievement rates of target attainment of AUC/MIC using Monte Carlo simulation (MCS). Two doses of pazufloxacin mesilate (PZFX) between q.d. and b.i.d. were compared for each species of bacterium. Concentrations for AUC of PZFX of 8 patients were measured at this hospital, and those from a phase I clinical study (phase I, 6 healthy volunteers) were used. MICs of PZFX were determined for each species of bacterium of respiratory organ origin (Pseudomonas aeruginosa, Haemophilus influenzae, Streptococcus pneumoniae, and Klebsiella pneumoniae). AUC per day of 500 mg b.i.d. used twice AUC (PZFX 500 mg x 2/day by patient, PZFX 500 mg x 2/day by phase I). Target attainment of AUC/MIC was AUC/MIC > or = 30 in S. pneumoniae and AUC/MIC > or = 125 in the other species of bacteria (P. aeruginosa, H. influenzae, and K. pneumoniae). As a result, patients showed an about 3 times higher AUC than the phase I subjects (67.9/21.9 microg/mL). In addition, the target attainment of AUC/MIC showed the highest rate in PZFX 500 mg x 2/day in patients with each type of bacteria: H. influenzae (98%), K. pneumoniae (89%), S. pneumoniae (66%), and P aeruginosa (41%). Target attainment of AUC/MIC was H. influenzae (91%), K. pneumoniae (81%), P. aeruginosa (5%), and S. pneumoniae (0%) in phase I. Therefore, the effectiveness of PZFX was estimated to be low using the MCS method with the phase I data.
authors.affiliation: Department of Clinical Pathology, Tenri Hospital.
authors.forename: Noriuyuki
authors.initials: N
authors.lastname: Abe
authors.forename: Saori
authors.initials: S
authors.lastname: Fukuda
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nakamura
authors.forename: Yosio
authors.initials: Y
authors.lastname: Taguchi
authors.forename: Shuji
authors.initials: S
authors.lastname: Matsuo
mesh_terms: D000293:Adolescent; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D017714:Community-Acquired Infections / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000302:isolation & purification; D009010:Monte Carlo Method; D010078:Oxazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D018410:Pneumonia, Bacterial / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000302:isolation & purification; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D024841:Fluoroquinolones; D010078:Oxazines; C078052:pazufloxacin