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Application of Monte Carlo simulation to the PK/PD evaluation of Gatifloxacin (GAT) against streptococcus pneumoniae for the treatment of Otitis Media in children
Author(s) -
Costanzo C. D.,
Cirincione B.,
Ambrose P. G.,
Rubino C. M.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.281
Subject(s) - streptococcus pneumoniae , otitis , medicine , gatifloxacin , acute otitis media , population , microbiology and biotechnology , surgery , biology , antibiotics , environmental health , ciprofloxacin
Purpose The PK/PD of GAT against S.pneumoniae in children with otitis media has not previously been explored. However, it has been demonstrated for quinolones against S. pneumoniae in non‐clinical infection models and in patients with community‐acquired respiratory tract infection that f AUC:MIC ratios greater than 30 are predictive of efficacy. These simulations used existing PK and MIC data to estimate the probability of attaining the PK/PD target of 30 in the general pediatric population after administration of GAT 10mg/kg for otitis media. Methods A 10,000–patient population was simulated with an age distribution similar to two Phase 2 studies. Height and weight were simulated using CDC growth charts. GAT exposure was simulated using the population PK model for GAT in plasma and middle‐ear fluid (MEF). The GAT MIC distribution for S. pneumoniae was derived from the SENTRY Antimicrobial Surveillance Program with MIC 50/90 of 0.25/0.5 (range: 0.03‐8.0). Simulated f AUC:MIC ratios were generated for each patient. Results For S. pneumoniae , the probability of attaining a f AUC 24 :MIC ratio of 30 was 95.5% (95% CI = 95.1–95.9%). (See Table) Conclusions The probability of PK/PD target attainment for GAT against S.pneumoniae was approximately 95%, thus supporting the use of GAT for the treatment of otitis media in children. Clinical Pharmacology & Therapeutics (2004) 75 , P74–P74; doi: 10.1016/j.clpt.2003.11.281Mean (SD) Minimum Median MaximumAUC 0–24 Plasma 26.8 (8.56) 7.15 25.5 93.3 MEF 26.7 (8.55) 7.13 25.4 93.1f AUC 24 :MIC Plasma 106 (115) 1.65 77.6 680 MEF 106 (115) 1.64 77.5 679