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Population pharmacokinetics and pharmacodynamics of sitafloxacin in patients with community-acquired respiratory tract infections.

Tanigawara Y, Kaku M, Totsuka K, Tsuge H, Saito A - J. Infect. Chemother. (2013)

Bottom Line: As a result of the univariate logistic regression analysis, the larger the value of fAUC(0-24h)/MIC or fC max/MIC becomes, the higher the bacteriological efficacies.The eradication rates for fAUC(0-24h)/MIC ≥ 30 and for fC max/MIC ≥ 2 were 96.4% and 96.3%, respectively.Furthermore, a 100 mg once-daily regimen was expected to show similar efficacy based on the PK-PD simulations.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacokinetics and Pharmacodynamics, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan, tanigawara-yusuke@umin.ac.jp.

ABSTRACT
An optimal dosage regimen of sitafloxacin was considered based on a pharmacokinetics and pharmacodynamics (PK-PD) analysis in patients with community-acquired respiratory tract infections (RTI). A population pharmacokinetic analysis of sitafloxacin was conducted using clinical data of five clinical pharmacology studies and one clinical PK-PD study in patients with RTIs. The pharmacokinetic parameters in individual patients were estimated by the Bayesian method to examine any correlation between pharmacokinetics and bacteriological efficacy. Efficacy data were obtained from the clinical PK-PD study, in which 50 or 100 mg sitafloxacin was administered twice daily for 7 days. In addition, an efficacy was simulated for a hypothetical dose regimen of 100 mg once daily. The fAUC(0-24h)/MIC and the fC max/MIC of sitafloxacin at a dose of 50 mg twice daily were 117.5 ± 78.0 and 7.3 ± 4.7 (mean ± SD), respectively. As a result of the univariate logistic regression analysis, the larger the value of fAUC(0-24h)/MIC or fC max/MIC becomes, the higher the bacteriological efficacies. The eradication rates for fAUC(0-24h)/MIC ≥ 30 and for fC max/MIC ≥ 2 were 96.4% and 96.3%, respectively. The PK-PD target values of sitafloxacin for the treatment of mild to moderate RTIs were considered to be fAUC(0-24h)/MIC ≥ 30 and fC max/MIC ≥ 2. The PK-PD parameters at the regimen of 50 or 100 mg twice daily in patients with RTIs reached the target values. Furthermore, a 100 mg once-daily regimen was expected to show similar efficacy based on the PK-PD simulations.

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Related in: MedlinePlus

Associations between bacteriological efficacy and pharmacokinetics and pharmacodynamics (PK–PD) variables (univariate logistic regression; number of strains used for evaluation = 91)
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Fig3: Associations between bacteriological efficacy and pharmacokinetics and pharmacodynamics (PK–PD) variables (univariate logistic regression; number of strains used for evaluation = 91)

Mentions: As a result of an univariate logistic regression analysis, larger values of fAUC0–24h/MIC or fCmax/MIC were shown to be correlated with a higher bacteriological efficacy of sitafloxacin. The effects of the PK–PD parameters were statistically significant (Fig. 3).Fig. 3


Population pharmacokinetics and pharmacodynamics of sitafloxacin in patients with community-acquired respiratory tract infections.

Tanigawara Y, Kaku M, Totsuka K, Tsuge H, Saito A - J. Infect. Chemother. (2013)

Associations between bacteriological efficacy and pharmacokinetics and pharmacodynamics (PK–PD) variables (univariate logistic regression; number of strains used for evaluation = 91)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3824208&req=5

Fig3: Associations between bacteriological efficacy and pharmacokinetics and pharmacodynamics (PK–PD) variables (univariate logistic regression; number of strains used for evaluation = 91)
Mentions: As a result of an univariate logistic regression analysis, larger values of fAUC0–24h/MIC or fCmax/MIC were shown to be correlated with a higher bacteriological efficacy of sitafloxacin. The effects of the PK–PD parameters were statistically significant (Fig. 3).Fig. 3

Bottom Line: As a result of the univariate logistic regression analysis, the larger the value of fAUC(0-24h)/MIC or fC max/MIC becomes, the higher the bacteriological efficacies.The eradication rates for fAUC(0-24h)/MIC ≥ 30 and for fC max/MIC ≥ 2 were 96.4% and 96.3%, respectively.Furthermore, a 100 mg once-daily regimen was expected to show similar efficacy based on the PK-PD simulations.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacokinetics and Pharmacodynamics, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan, tanigawara-yusuke@umin.ac.jp.

ABSTRACT
An optimal dosage regimen of sitafloxacin was considered based on a pharmacokinetics and pharmacodynamics (PK-PD) analysis in patients with community-acquired respiratory tract infections (RTI). A population pharmacokinetic analysis of sitafloxacin was conducted using clinical data of five clinical pharmacology studies and one clinical PK-PD study in patients with RTIs. The pharmacokinetic parameters in individual patients were estimated by the Bayesian method to examine any correlation between pharmacokinetics and bacteriological efficacy. Efficacy data were obtained from the clinical PK-PD study, in which 50 or 100 mg sitafloxacin was administered twice daily for 7 days. In addition, an efficacy was simulated for a hypothetical dose regimen of 100 mg once daily. The fAUC(0-24h)/MIC and the fC max/MIC of sitafloxacin at a dose of 50 mg twice daily were 117.5 ± 78.0 and 7.3 ± 4.7 (mean ± SD), respectively. As a result of the univariate logistic regression analysis, the larger the value of fAUC(0-24h)/MIC or fC max/MIC becomes, the higher the bacteriological efficacies. The eradication rates for fAUC(0-24h)/MIC ≥ 30 and for fC max/MIC ≥ 2 were 96.4% and 96.3%, respectively. The PK-PD target values of sitafloxacin for the treatment of mild to moderate RTIs were considered to be fAUC(0-24h)/MIC ≥ 30 and fC max/MIC ≥ 2. The PK-PD parameters at the regimen of 50 or 100 mg twice daily in patients with RTIs reached the target values. Furthermore, a 100 mg once-daily regimen was expected to show similar efficacy based on the PK-PD simulations.

Show MeSH
Related in: MedlinePlus