Pharmacokinetics of ofloxacin in drug-resistant tuberculosis.
The pharmacokinetics of ofloxacin were investigated in 11 drug-resistant pulmonary tuberculosis (TB) patients with a mean age (SD) of 38.09 (11.97) years. All patients received ofloxacin 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 ofloxacin concentrations were determined by high performance liquid chromatography (HPLC) assay. Pharmacokinetics of ofloxacin 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 microg/ml occurred at 1.68 +/- 1.21 hours. Means +/- SD of AUC(0-24) and AUC(0-infinity) were 70.57 +/- 26.40 and 82.45 +/- 43.64 microg x h/ml, respectively. Ofloxacin distributed widely with a mean +/- SD of Vss/F of 1.37 +/- 0.24 L/kg. Mean +/- SD of CL/F was 8.19 +/- 2.53 L/h, whereas mean +/- SD of T(1/2beta) and mean residence time were 8.03 +/- 3.37 and 10.77 +/- 4.55 hours, respectively. The free Cmax/MIC of Mycobacterium tuberculosis of 7.7-15.4:1 was estimated. These suggested that ofloxacin 10 mg/kg once daily combined with other active anti-TB drugs provides sufficient Cmax/MIC ratio and long T(1/2beta) which supported its use in drug-resistant TB.
Chulavatnatol
Suvatna
S
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
Chindavijak
Busba
B
Chierakul
Nitipatana
N
Klomsawat
Duangrat
D
D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004359:Drug Therapy, Combination; D006801:Humans; D008875:Middle Aged; D015242:Ofloxacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011718:Pyrazinamide / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
D000890:Anti-Infective Agents; D000995:Antitubercular Agents; D011718:Pyrazinamide; D015242:Ofloxacin; D012293:Rifampin