Pharmacokinetics of Ofloxacin in Drug-Resistant Thber culosis

SUV ATNA CHULA VA TNA TOL, PhD*, BUSBA CHINDA VIJAK, PhD*, NITIPATANA CHIERAKUL, MD, FRCP**, DUANGRAT KLOMSAWAT, BS*

Affiliation : * Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, ** Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

AbstractThe pharmacokinetics of otloxacin were investigated in 11 drug-resistant pulmonary tuber culosis (TB) patients with a mean age (SO) of 38.09 (11.97) years. All patients received otloxacin 10 mg/kg once daily combined with other active anti-TB drugs. Following an 8-h overnight fast, serum samples were drawn prior to and from 0.25 up to 24 hours after dosing. Serum otloxacin concentrations were determined by high performance liquid chromatography (HPLC) assay. Pharmacokinetics of otloxacin were well described by a linear, 2-compartment open model with first-order absorption and first-order elimination. Mean± SD of Cmax was 9.61 ± 2.17 ~g/ml occurred at 1.68 ± 1.21 hours. Means± SD of AUC _ and AUC _ were 70.57 ± 26.40 and 82.45 ± 43.64 ~g x 024 0 h/ml, respectively. Ofloxacin distributed widely with a mean± SD of VjF of 1.37 ± 0.24 L/kg. Mean± SD of CL/F was 8.19 ± 2.53 L/h, whereas mean ± SD of T112~ and mean residence time were 8.03 ± 3.37 and 10.77 ± 4.55 hours, respectively. The free CmJMIC of Mycobacterium tuberculosis of7.7-15.4: 1 was estimated. These suggested that ofloxacin 10 mg/kg once daily combined with other active anti TB drugs provides sufficient Cm ..I MIC ratio and long T112~ which supported its use in drug-resistant TB.

Keywords : Ofloxacin, Pharmacokinetics, Drug-Resistant Tuberculosis

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