Pharmacokinetic/pharmacodynamic study of sparfloxacin
- VernacularTitle:司帕沙星的药代动力学与药效学研究
- Author:
Tong YU
1
;
Gan-Bin WU
;
Xiao-Tian LI
;
Yan-Le CHU
;
Ling-Xi WANG
Author Information
1. 郑州大学 药学院 药理系
- Keywords:
sparfloxacin;
minimum inhibitory concentration;
Monte Carlo;
pharmacokinetic;
pharmacodynamic
- From:
The Chinese Journal of Clinical Pharmacology
2014;(8):681-684
- CountryChina
- Language:Chinese
-
Abstract:
Objective To optimize clinical dosage regimen of sparfloxa-cin through series of pharmacokinetic/pharmacodynamic ( PK/PD ) val-ues.Methods The minimum inhibitory concentration ( MIC ) of spar-floxacin to 479 isolated bacteria were measured by two -fold agar dilution method.To perform pharmacokinetic test after those healthy volunteers were given a single oral dose of 0.1 , 0.2 , 0.3 g of Sparfloxacin , respec-tively.Based on PK/PD theory, calculation of AUC0-24 h/MIC values af-ter three dosages were done.Estimated value of AUC 0-24 h/MIC≥125 was expected to be the target value ( for streptococcus pneumoniae AUC0-24 h/MIC≥50).The Monte Carlo simulation was repeated 1 ×104 times, and the cumulative fraction of response ( CFR) value was calculat-ed according to the respective probability distributions and different AUC0-24 h/MIC and MIC values.The dosage achieving a CFR above 90 percent was recognized as the optimal dosage regimen.Results Given dose of 0.1 g, the pharmacodynamics value CFR was above 90%only to salmonella genera.Given dose of 0.2 g, the pharmacodynamics value CFR was above 90%to Nitrate negative bacillus, Streptococcus pneumoni-ae, Acinetobacter and Methicillin -sensitive Staphylococcus aureus (MSSA).For other strains, oral dose of 0.3 g was needed to not only achieve satisfactory clinical curative effect but also effectively prevent the drug resistance.And for infections caused by Methicillin -resistant Staphylococcus aureus (MRSA), enhanced drug dose should be considered to achieve satisfactory clinical efficacy.Conclusion For infection caused by salmonella genera, oral dose of 0.1 g was a appropriate dosage regimen.For infection caused by Nitrate negative bacillus, Strepto-coccus pneumoniae, Acinetobacter and MSSA, oral dose of 0.2 g was a proper dosage regimen.For infection caused by others, oral dosage regimen of 0.3 g could achieve the expected satisfactory clinical efficacy.And for infections caused by MRSA, an increasing dosage , such as 0.4 mg, could achieve satisfactory clinical curative effect.
