Pharmacokinetics of ofloxacin in patients with multidrug-resistant tuberculosis

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 frequently 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: 18.5≤BMI<23, group B: BMI<18.5). Blood 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±8.9μg/ml·h vs. 24.1± 6.2μg/ml·h) (Check the symbols), (p<0.05). The total clearance (Cl/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 ofloxaicn in chronic debilitated MDR-Tb patients.