Pharmacokinetics of ofloxacin in Patients with Multidrug-Resistant Tuberculosis / 결핵

ABSTRACT

BACKGROUND: There are few studies that have reported on the pharmacokinetic(PK) disposition of fluoroquinolones in patients with multi-drug resistant tuberculosis(MDR-Tb), even though fluoroquinolones are frequentl y co-prescribed to those patients. In this study, the PK disposition of ofloxacin, a fluoroquinolone, was evaluated in patients with MDR-Tb. METHODS: Twenty patients with MDR-Tb were given 2nd line Tb drugs including ofloxacin (300mg twice a day), prothionamide, cycloserine, para-aminosalicylic acid, kanamycin, and streptomycin. The patients were grouped according to their body mass index(BMI) as an index of emaciation (group A 18.5Blood samples were serially drawn and urine samples were collected upto 24 hours after the last dose of those drugs at steady state (over 1 month). The ofloxacin concentrations were determined using HPLC (High Performance Liquid Chromatography).

RESULTS:

The AUC of ofloxacin in group B was greater than that in group A (31.4+/-8.9micro gram/ml.h vs. 24.1+/-6.2micro gram/ml.h)(Check the symbols),(p<0.05). The total clearance(CI/F) of ofloxacin was 0.16+/-0.03 l/h/kg in group A, and 0.14+/-0.03 l/h/kg in group B. The half-lives of ofloxacin in two groups were similar (group A 5.3+/-0.8 hours, group B 5.7+/-0.9 hours). In addition, the other PK parameters in two groups were also similar.

CONCLUSIONS:

The pharmacokinetics of ofloxacin in patients with MDR-Tb appears to be comparable with those of normal subjects, and the extent of emaciation appears to have an influence on the pharmacokinetics of ofloxacin in chronic debilitated MDR-Tb patients.