Determination of plasma concentrations using LC/MS and pharmacokinetics of ofloxacin in patients with multi-drug resistant tuberculosis and in patients with multi-drug resistant tuberculosis coinfected with hiv
Many studies have investigated the pharmacokinetics of anti-tuberculosis drugs in patients infected with tuberculosis. However, little is known about the pharmacokinetics of the drugs that are used in the treatment of multi-drug resistant tuberculosis (MDRTB).Therefore, the objective of the present study was to investigate the steady state concentrations and the pharmacokinetics of ofloxacin, one of the drugs used in the treatment of MDR-TB in patients infected with MDR-TB and patients with MDR-TB co-infected with HIV Plasma samples were drawn at different times over 24 hours after ofloxacin oral administration. For the determination of ofloxacin plasma concentrations, the liquid chromatography coupled with mass spectrometry analysis method was used.The method was validated over a concentration range of 0.1-10 μg/ml. The lower limit of ofloxacin detection was 0.05μg/ml, while the lower limit of quantification was 0.1μg/ml. The response was linear over the range used with a mean recovery of 97.6%. Ofloxacin peak was well separated at a retention time of 9.6 minutes.The pharmacokinetic parameters obtained were presented as mean ± standard deviation(SD). The peak concentration of ofloxacin (Cmax) was 4.71± 2.27 μg/ml occurred at Tmax 3±1.29 hours after ofloxacin oral administration. The mean (±SD) for the area under the concentration-time curve (AUC0-24) and the area under the concentration-time curve(AUC0-∞) were 68.8±42.61 μg/ml.hr and 91.93±76.86 μg/ml.hr, respectively. Ofloxacin distributed widely with a mean (±SD) volume of distribution (Vd) 2.77±1.16 L/kg and it was eliminated with a mean (±SD) total clearance rate of 0.27±0.25 L/hr/kg. Ofloxacin mean (±SD) half-life was 9.55± 4.69 hours and mean (±SD) of the mean residence time (MRT) was 1512± 6.59 hours.In summary, compared with the previous findings in the literature, ofloxacin pharmacokinetic was altered in MDR-TB patients with or without HIV co-infection.The AUC and Cmax were reduced, while the half-life and the time to reach the peak concentration were prolonged. This suggests that, both the rate and the extent of ofloxacin absorption were decreased. Furthermore, ofloxacin was highly eliminated in patients, which may be related to the altered liver function in this group of patients.Further studies investigating the effect of HIV, liver and kidney dysfunctions on ofloxacin pharmacokinetics are recommended in large number of patients infected with MDR-TB.in addition to the therapeutic drug monitoring to maintain the desired concentration of ofloxacin in the patients.